Insulin resistance and hyperinsulinemia occur more frequently in subjects with greater visceral adiposity, but it is not known whether these metabolic abnormalities precede or follow visceral fat accumulation. We prospectively studied the development of visceral adiposity in relation to fasting and stimulated insulin and C-peptide levels. We followed 137 nondiabetic, second-generation Japanese-American men for changes in visceral adiposity over 5 years. Intra-abdominal fat (IAF) area (square centimeters) was measured at the umbilicus by computed tomography at baseline and after 5 years. Plasma insulin and C-peptide levels were measured after an overnight fast and during an oral glucose tolerance test. Beta-cell function was measured by the insulin secretion ratio (30-0 min plasma insulin difference)/(30-0 min plasma glucose difference). After adjustment for baseline IAF in multiple linear regression models, baseline fasting insulin (coefficient = 0.241, P = 0.048) and C-peptide (coefficient = 38.538, P < 0.001) levels were positively correlated, while the baseline insulin secretion ratio was negatively correlated with IAF change (coefficient = -0.099, P = 0.027). With IAF difference coded as a dichotomous variable (> 0 cm2 vs. < or = 0 cm2), the highest versus lowest tertile of baseline fasting insulin (odds ratio [OR] = 3.0, 95% CI 1.0-9.7) and fasting C-peptide (OR = 8.1, 95% CI 2.4-26.8) levels and the lowest versus highest tertile of the insulin secretion ratio (OR = 3.3, 95% CI 1.0-10.0) were associated with higher odds of IAF gain. Greater insulin resistance and reduced insulin secretion precede visceral fat accumulation in nondiabetic Japanese-American men.