Five normally cycling healthy women were given daily subcutaneous injections of human leukocyte interferon (3 × 106 units/day) from the 3rd through 23rd day of the menstrual cycle, and serum steroid and peptide hormone concentrations monitored at 3-day intervals during the treatment and the preceding control cycle. Concentrations of cytosol and nuclear estrogen receptors (ERc and ERn, respectively) and progestin receptors (PRc and PRn) were also measured from endometrial biopsies taken on the 24th day of the control and treatment cycle. In addition, an extensive monitoring of clinical chemical and hematological tests from the blood samples were performed. Serum estradiol and progesterone concentrations were significantly decreased during the treatment cycle, suggesting that interferon interacts in vivo with the function of both FSH and LH. No significant changes were observed in the serum peptide hormone concentrations measured (FSH, LH, prolactin, insulin, growth hormone and TSH); neither were the levels of endometrial ERc, ERn, PRc and PRn affected by interferon administration. As expected, interferon administration resulted in decreased leukocyte counts. Moreover, an increasing tendency in the activities of serum alkaline phosphatase and gamma-glutamyltransferase during the interferon therapy shows that interferon may slightly interfere with the liver function. These results suggest that one of the mechanisms by which interferon treatment may affect the growth of hormone-dependent neoplasms could be the interaction with production and/or function of circulating hormonal compounds.