The acute effects of hyperinsulinemia on androgen homeostasis and a possible association of androgens to insulin sensitivity, serum lipids and lipoproteins and to lipid oxidation were examined in 19 healthy males (27 ± 1 yrs, body mass index 24 ± 1 kg/m2). In each subject, a 240 min euglycemic hyperinsulinemic clamp was performed and glucose and lipid oxidation were determined by indirect calorimetry. During hyperinsulinemia serum sex hormone-binding globulin (SHBG) concentration decreased by 5% (P<0·01), insulin-like growth factor binding protein (IGFBP-1) by 88% (P<0·001) and dehydroepiandrosterone sulphate (DHEAS) by 12% (P<0·001), with no change in total or free testosterone concentrations. In the basal state, IGFBP-1 and C-peptide were inversely related (r= −0·54, P<0·05). Fasting concentrations of serum free testosterone (r=0·59, P<0·01) and DHEAS (r=0·47, P<0·05) correlated positively with serum free fatty acid (FFA) concentrations during hyperinsulinemia, but not with fasting FFA level. Lipid oxidation rate in the basal state correlated positively to the decline in SHBG (r=0·61, P<0·01) and DHEAS concentrations (r=0·62, P<0·01) during hyperinsulinemia. While the fasting serum high density lipoprotein cholesterol level correlated positively with the insulin-induced decline in DHEAS level (r=0·58, P<0·01), no associations were found between serum androgens and total cholesterol, low density lipoprotein cholesterol or triglyceride concentrations. Insulin sensitivity was not related to SHBG, IGFBP-1, DHEAS or testosterone concentrations. It is concluded that, in the healthy man with normal androgen homeostasis, (1) acute hyperinsulinemia decreases SHBG, IGFBP-1 and DHEAS concentrations, (2) the relative insulin-induced decline of IGFBP-1 level is 18-fold greater than that of the SHBG level, (3) androgens may maintain lipolysis during hyperinsulinemia and (4) there is no association between physiological androgen concentrations and insulin sensitivity.