In a previous study performed in adult obese and normal-weight male subjects, we found that suppression of insulin levels by diazoxide reduced testosterone and increased sex hormone-binding globulin (SHBG) blood concentrations. These and other data suggested that insulin may have a regulatory capacity in testosterone secretion and/or metabolism in men, similar to what has already been demonstrated in women. In this study, we investigated the effects of acute hyperinsulinemia on major androgen levels, including testosterone, in two groups of normal-weight in = 11) and obese (n = 9) men. Acute hyperinsulinemia was obtained by the euglycemic-hyperinsulinemic clamp technique. Relationships between the degree of insulin resistance (ie, total glucose disposal [M value]) and testosterone levels were also evaluated. Basal testosterone levels in obese subjects (10.40 +/- 3.02 nmol/L) were significantly lower than in normal-weight controls (15.50 +/- 4.65 nmol/L, P < .01), whereas no difference was present in androstenedione and dehydroepiandrosterone sulfate (DHEA-S) concentrations. During the clamp study, testosterone was significantly increased in the obese group (11.79 +/- 3.64 nmol/L, P < .05) but not in the control group (15.81 +/- 4.54 nmol/L, P = NS). The other two androgens did not significantly change in either the obese or control group. There was a highly significant correlation between baseline testosterone concentrations, with M values suggesting a relationship between impaired peripheral insulin sensitivity and reduced plasma testosterone concentrations. It should be pointed out that there was a certain discrepancy in the testosterone variations, particularly in the control group, in which two thirds of the subjects had no change or some decrease in testosterone levels, whereas in the remainder testosterone increased over the values of the assay variation coefficient. These findings are consistent with the hypothesis that insulin may regulate testosterone blood levels also in male subjects. Whether these effects are primarily due to increased hormone secretion or reduced clearance needs to be investigated.