The study was performed to determine plasma levels of proinsulin (PI) and specific insulin (SI) in normoglycemic (NGT) Asian Indians and to assess the effect of obesity and impaired glucose tolerance (IGT) on these concentrations. Blood samples from 151 adult nondiabetic South Indian subjects were collected during an epidemiological survey of diabetes. Plasma SI and PI levels were measured in fasting and 30-minute and 120-minute samples of a glucose tolerance test (World Health Organization criteria) using monospecific antibodies. The total insulin (TI) level was also measured by the nonspecific assay. The molar ratio of PI to SI (PI/SI) was calculated. Correlations of the peptides with anthropometry, serum lipids, and blood pressure (BP) were studied by univariate and multivariate analyses. Comparisons were also made in NGT versus IGT groups. As expected, TI values were higher than SI values, but the patterns of response were similar for both. SI and PI responses in NGT were similar to the values found in Mexican-Americans who had a higher body mass index (BMI). Asian Indians were thus found to have a high SI response despite a low BMI. Obesity and IGT produced an increased response of both PI and SI, with normal PI/SI ratios thus showing an absence of hyperproinsulinemia in either condition. Fasting PI showed a strong association with serum triglycerides, and proinsulin at 120 minutes was associated with cholesterol. None of the peptides showed a correlation with BP. Using specific assays for insulin and PI, it is shown that Asian Indians with NGT have a hyperinsulinemic response despite a low BMI. Obesity and mild hyperglycemia in IGT produce a simultaneous increase in PI and SI with no alteration in the PI/SI ratio.