29 growth had developed atrophy of the thyroid gland before puberty, and changes associated with puberty were delayed. There may be someassociation between the apparent increased demandfor thyroid hormone at puberty and the appearance of thyroid nodules, since in 10 children (4 males and 6 females) thyroid nodules appeared near the expected or actual time of puberty. In 5 other children (2 males and 3 females) the nodules appeared | to 3 years after puberty and in the females were associated with pregnancies. In evaluating the influence of puberty and pregnancyit should be pointed out that the latent period between exposure andthe developmentof thyroid abnormalities was fairly constant in all these children, varying between 10 and [3 years, so that the abovefindings may have beenfortuitous. In the 4 women who developed carcino:-a of the thyroid the possible influence of the stress of pregnancy mustbe considered, since al] had multiple pregnancies in the years preceding the developmentoflesions. Sex incidence The sex ratio of occurrence of benign thyroid lesions in the Rongelap population was 1.3 in females to 1.0*in males. This may be misleading since, in the group exposed at <10 years of age, all the females had lesions whereas 2 males did not. The fact that all 3 malignant lesions of the thyroid were in females is consistent with reported statistics showing a preponderance of suchlesions in females,?6 Discussion By the time the first malignant thyroid lesion appearedin the more heavily exposed Rongelap group several years ago, numerous benign adenomatous thyroid nodules had appeared. The latter were suspected of being related to the radiation exposure, but such an etiological relationship of the single isolated malignant lesion found at that time was speculative. The finding of 2 additional individuals with thyroid carcinomain this group (3 among21 thyroid lesions in 67 Rongelap people exposed) makes theetiological role of radiation exposure increasingly probable. For the time being the single malignant thyroid lesion found in a woman from Utirik Atoll cannot be attributed to radiation exposure because of the low dose received there. Thesignificance of radiation exposure of the thyroid glands in the Rongelap people had not been fully appreciated until the appearance of thyroid lesions. More careful review of the dose calculations indicated that considerable exposures from radioactive iodine absorption had probably occurred, particularly in the children. The exposure of the Rongelap people was not comparable with exposure of populations due to fallout from reactor accidents in which radionuclides are absorbed chiefly via milk from cattle grazing on con- taminated pastures. The Marshall Islands have no cattle and no local milk supply. (Mother’s milk may have contributed to the radioiodine absorption in 2 children reported to have been nursing at the time of the accident.) But there was heavy contamination of food and water supplies on Rongelap and a relative abundance of radioiodines in the fallout. The dose to the thyroid glands was greater than that to other organs bya factor of 2 in adults and a factor of about 7 in children. Numerous animalstudies have demonstrated the role of radiation in the etiology of thyroid neoplasms.*7-29 In humans the development of thyroid nodules and cancerfrom x-irradiation,30.31 particularly when the radiation occurs in infancy and childhood,32-44 is well documented. Develop- mentof such lesions from radioiodines has also been seen in animals but less frequently in hu’ mans. Shelineet al.3° reported 8 cases of nodular goiter in their follow-up study of 250 cases treated for hyperthyroidism. Six of these cases were irradiated before 20 years of age and 4 before 10 years of age. One showed a possible invasion of the thyroid capsule. The incidence of thyroid nodularity in the exposed Marshallese is considerably higher than that reported by Pincus?? and Hempelmann**in their studies of populations who had been exposed to therapeutic x-irradiation of the neck region ata young age. However,on a risk per rad basis, the incidence of 51 cases per 108 persons per rad per year for the Marshallese is quite comparable with 24 for one group and 64 for a second group calculated by Pincus and Hempelmann. This comparison seemsto indicate similar effectiveness — per rad ~ of x-radiation and radioiodine exposure.* The 3 malignantlesions of the thyroid reported here in the heavily exposed Rongelap people appear to be the first such cases clearly associated with radioiodine exposure except for one possibly malignantthyroid lesion reported by Sheline et al.3° *Mr. Keith Thompson of this Laboratory carried out the Statistical analyses in the thyroid cases.