The effect of isotretinoin (Roaccutane) on serum steroids and urinary steroid metabolites was investigated in seven female patients receiving the drug for treatment of severe acne over a 16-week period. Serum concentrations of dehydroepiandrosterone sulphate (DHAS), androstenedione (A2), and free androgen index (FAI) were not significantly altered. There was a significant fall in testosterone during treatment and a significant reduction in the 24 h urinary excretion of androsterone, tetrahydrocortisone (THE) and tetrahydrocortisol (THF) from week 8 onwards and for aetiocholanolone and allo-THF from week 12 (P less than 0.05). Although pretreatment levels of urinary steroid metabolites were not abnormal, the ratios of the 5 alpha/5 beta metabolites (androsterone:aetiocholanolone and allo-THF:THF) were at the upper limit of the reference range and were lowered after treatment, suggesting that 5 alpha-reductase activity is sensitive to isotretinoin.