We have measured thyroid hormone levels, TSH and prolactin (PRL) pituitary reserve in 27 patients with longstanding untreated endemic cretinism living in an isolated village in Central Brazil where severe iodine deficiency still exists. Alpha subunit and TSH-β levels were also measured basally and after the administration of thyrotropin-releasing hormone (TRH). The patients were clinically divided into 3 groups: hypothyroid cretins (group I), goitrous neurological cretins (group II), and neurological cretins without goiter (group III). Seven of the hypothyroid patients had an enlarged sella turcica, but none of the patients with neurological cretinism. Only group I patients had significantly lower mean T4 (4.8 ±0.6 μg/dl) and T3 (60±8 ng/dl) levels and higher TSH levels (46 ± 24 μU/ml) than normal individuals, but T3 concentrations were also lower than normal in group II (78±4ng/dl)andgrouplll (101 ± 13 ng/dl) patients. Five patients in group II and 3 patients in group III had decreased thyroid reserve, as evidenced by elevated basal TSH levels and/or increased TSH responses to TRH. Two patients in group I and 1 in group III had moderately elevated basal PRL levels (16–25 ng/ml), but 10 patients demonstrated increased PRL responses to TRH ( >50 ng/ml). Alpha subunit concentrations were appropriate for age and thyroid status. Only 2 postmenopausal women in group 11 had slightly elevated levels at 7.8 and 8.0 ng/ml. Alpha and TSH-β responses to TRH were also appropriately related to the degree of hypothyroidism. Although most of the hypothyroid endemic cretins had enlarged sella turcicas, no clear cut evidence of a pituitary tumor was apparent. This sellar enlargement could merely be secondary to hyperplasia or hypertrophy of the pituitary TSH-secreting cells. Treatment of these patients with thyroid hormone should help elucidate whether any of these hypothyroid cretins have a pituitary tumor.