Serum androgen levels were studied in 100 patients (50 male) with varying degrees of severe illness, determined by Acute Physiological and Chronic Health Evaluation (APACHE). Comparison with normal subjects revealed the following changes: (1) Basal dehydroepiandrosterone sulphate (DHEAS) values were decreased in the ill female patients (P less than 0.001) as well as in the ill males (two groups, P less than 0.01; P less than 0.05). Androstenedione values did not differ from the controls in patients of either sex. Basal testosterone levels were decreased in ill male patients (P less than 0.001), but not in females. (2) The low testosterone concentrations in the severely ill male patients correlated inversely with the APACHE score; additionally, a dependence on diagnostic categories could be demonstrated in men, since the lowest values were found in patients suffering from sepsis or liver cirrhosis. Acutely ill males had a moderately decreased testosterone, whereas chronically ill males showed a marked reduction of testosterone compared to the controls. Lowered DHEAS and androstenedione levels could be measured in chronically ill males but not in ill females. (3) 17 alpha-OH-progesterone and 17 alpha-OH-pregnenolone levels in subgroups of the patients suggested a probable enzymatic block in the delta 5-pathway of androgen biosynthesis in severe illness. The ratio of 17 alpha-OH-pregnenolone to DHEAS was significantly higher in male patients and tended to be high in ill females, whereas the ratio of 17 alpha-OH-progesterone to androstenedione showed no difference between healthy and ill subjects.