The effect of body composition on clearance of infused insulin was studied in 21 young normal weight (relative body weight 107 +/- 2%, of ideal mean +/- SEM) healthy subjects. In each subject, the per cent of body weight made up of muscle and fat tissue (% muscle and % fat) were determined. Clearance of insulin was estimated during infusion of insulin at the rate of 40 mU/m2/min under maintenance of normoglycaemia using the euglycaemic clamp technique. Steady-state plasma insulin levels (92.6 +/- 3.2 mU/litre) correlated negatively with % muscle (r = -0.60, P less than 0.01), and positively with % fat (r = 0.55, P less than 0.01). Clearance of insulin was directly related to % muscle (r = 0.60, P less than 0.01), and inversely related to % fat (r = -0.48, P less than 0.01). Steady-state plasma insulin levels or insulin clearance did not correlate with relative body weight. Multiple linear regression analysis revealed a significant multivariate correlation between the rate of insulin clearance versus % muscle and % fat (r = 0.62, P less than 0.02). The changes in % muscle and % fat could predict 37% of the observed interindividual variance of insulin clearance. These results indicate that insulin clearance depends on body composition and is higher in muscular than in adipose subjects. This difference may reflect either a greater distribution space of insulin in muscular as compared to adipose subjects or an influence of body composition on insulin catabolism.