Ketoconazole is an orally active antimycotic agent and a potent inhibitor of gonadal and adrenal steroidogenesis. As inhibitor of steroid production, it has been employed in Cushing's syndrome, prostatic cancer and precocious puberty due to autonomous Leydig-cell hyperfunction. By virtue of its selective action on androgen synthesis at low doses by inhibition of C17-20 lyase, this drug could be of potential therapeutic utility in hirsutism. We evaluated the hormonal and clinical effects of a low-dose regimen (400 mg/day) for 3 months in 16 women with a spectrum of disorders from idiopathic hirsutism to polycystic ovary syndrome. Four of them completed 6-month treatment. At 3 months, DHEA-S decreased from 9.9 +/- 1.0 (mean +/- SE) to 6.9 +/- 1.0 mumol/L (p less than 0.01), androstenedione from 13.3 +/- 1.5 to 8.3 +/- 1.3 nmol/L (p less than 0.005), and testosterone from 4.2 +/- 0.4 to 3.1 +/- 0.4 nmol/L (p less than 0.05). No significant changes were observed in LH, FSH, prolactin and estradiol levels. In patients treated for 6 months, androgens were within normal limits at the end of the study. Eleven out of 16 women (about 70%) reported some improvement in their hirsutism. There was a significant decrease in Ferriman-Gallwey's score (p less than 0.001) and mean hair-shaft diameter (p less than 0.001). The patients treated for 6 months showed a further improvement. Pelvic ultrasonography, when repeated (n = 8), was either unchanged or improved. Side effects (polymenorrhea, gastrointestinal reaction, somnolence) were generally mild and transient. Of 20 women who entered the study the dropout rate was 20% (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)