Profound biological changes occur in patients treated with interferon. Observations of endocrine changes prompted us to examine the effects of subcutaneous alpha-interferon administration in single doses on circulating levels of thyroid stimulating hormone, total thyroxine, and total triiodothyronine in 10 volunteers (5 healthy subjects and 5 patients with hepatitis C). Blood samples were taken on an out-patient basis immediately before and 2, 12, 24, 48, and 72 h after administration of 1, 3, or 5 x 10(6) units of recombinant alpha-interferon. Application of the different dose levels was randomly assigned. Plasma samples were stored at -80 degrees C; after collection of samples had been completed hormone levels were measured using commercially available test kits. At all time points before and after injection of alpha-interferon, standard deviations of measured hormone levels of healthy control subjects and patients overlapped to a considerable extent. At a dose level of 5 x 10(6) units, alpha-interferon significantly increased cortisol levels as described, and decreased the level of thyroid stimulating hormone in the group receiving alpha-interferon as compared to placebo-treated healthy volunteers. The effects occurred 12 h after injection. Maximum suppression of thyroid stimulating hormone levels was observed 24 h after injection, when serum levels of thyroxine and triiodothyronine also were significantly reduced. We conclude that subcutaneous alpha-interferon treatment with doses as low as 5 x 10(6) units affects the control of thyroid function.