This study investigated the chronic effects of interferon-alpha 2 (IFN-alpha 2) on hormonal secretion in humans. Six patients suffering from chronic hepatitis B or C infection received SC doses of 3 million IU IFN-alpha 2 three times a week for 4 mo. Each patient was examined for hormone secretion four times: the day before initial IFN-alpha 2 administration (day 0), the day of the first injection (day 1), and 4 wk after start of IFN therapy on days 27 (without IFN administration) and 28 (with IFN administration). Adrenocorticotrophic hormone (ACTH), cortisol, growth hormone (hGH), and prolactin (PRL) were measured in plasma samples drawn at 30-min intervals between 1600h and 2400h. Acute administration of IFN-alpha 2 stimulated the release of ACTH to 423% (p = 0.02 vs. day 0) and cortisol to 393% (p = 0.01 vs. day 0) of control values in each patient. In five of the six patients, the plasma levels of hGH were higher on day 1 than on day 0. IFN-alpha 2 did not affect the secretion of prolactin. On day 27, the plasma levels of the four hormones were similar to the baseline levels on day 0. When IFN-alpha 2 was given on day 28, there were no significant differences in the release of ACTH (135% of control, p = 0.4) or cortisol (124% of control, p = 0.5) in comparison to day 27. These findings indicate that IFN-alpha 2 stimulation of hormone release is restricted to specific hormones.(ABSTRACT TRUNCATED AT 250 WORDS)