The aim of the present study was to assess whether 131I therapy for differentiated thyroid carcinoma (DTC) can affect endocrine testicular function. METHODS Serum follicle-stimulating hormone (FSH) and testosterone (T) concentrations were measured in 103 patients periodically submitted for radioiodine therapy for residual or metastatic disease. Mean follow-up was 93.7 +/- 54 mo (range 10-243 mo). RESULTS Mean FSH values in 131I-treated patients tested after their last treatment were 15.3 +/- 9.9 mU/ml, significantly higher than those of 19 untreated patients (6.5 +/- 3.1 mU/ml). Considering the mean +3 s.d. FSH of untreated subjects as the upper limit of normal range, 36.8% of the patients had an abnormal increase in serum FSH. Longitudinal analysis performed in 21 patients showed that the behavior of FSH in response to 131I therapy was not universal. Six patients had no change or a slight increase in serum FSH after 131I administration; eleven patients had a transient increase above normal values 6-12 mo after 131I treatment, with return to normal levels in subsequent months. The administration of a second dose was followed by a similar increase in FSH levels. Finally, four patients, followed for a long period of time and treated with several 131I doses, showed a progressive increase in serum FSH, which eventually became permanent. Semen analysis, performed in a small subgroup of patients, showed a consistent reduction in the number of normokinetic sperm. No change was found in serum T levels between treated and untreated patients. CONCLUSIONS Our results indicate that 131I therapy for thyroid carcinoma is associated with transient impairment of testicular germinal cell function. The damage may become permanent for high-radiation activities delivered year after year and might pose a significant risk of infertility.