OBJECTIVE: To determine in black and white youths the degree to which fatness and cardiovascular fitness (CVF) explained independent proportions of the variance in fasting insulin concentrations. STUDY DESIGN: Youths 14 to 18 years of age (n = 278) were studied. Insulin was measured after a 12-hour fast. Percent body fat (%BF) was measured with dual-energy x-ray absorptiometry. CVF was determined with a multistage treadmill test. RESULTS: Girls had higher %BF and lower CVF than boys. Whites were higher in CVF than blacks. There was a race by sex interaction for fasting insulin concentration, such that black girls had the highest and white girls had the lowest concentrations. When %BF and CVF was controlled statistically, this interaction was no longer significant. Multiple regression models that controlled for race, sex, and their interaction showed that (1) both higher %BF and lower CVF were significantly associated with higher insulin concentrations; (2) there were significant interactions with sex, such that the deleterious effects of low CVF and high %BF were greater in boys than in girls; (3) there was a significant CVF-%BF interaction, such that youths who were both fit and lean had especially low insulin concentrations; and (4) sex-specific regressions showed that both %BF and CVF explained significant independent proportion of the insulin variance for the boys but that only %BF did so for the girls. CONCLUSIONS: Interventions to prevent hyperinsulinemia in youths should be designed both to minimize fatness and maximize CVF.