Mexican Americans have an increased risk of non-insulin-dependent diabetes mellitus (NIDDM) relative to non-Hispanic whites which is only partially explained by their excess overall obesity and unfavourable body fat distribution. Non-diabetic Mexican Americans have hyperinsulinaemia and insulin resistance relative to non-Hispanic whites. We therefore hypothesized that the insulin resistance might be a more important predictor of NIDDM in high-risk populations characterized by obesity and insulin resistance, while compromised insulin secretion might be a more important risk factor for NIDDM in low-risk populations. We assessed the ability of ethnicity (Mexican American vs non-Hispanic white), age, overall adiposity (body mass index [BMI]), unfavourable body fat distribution (as assessed by waist-to-hip ratio [WHR]), glucose tolerance (impaired glucose tolerance vs normal glucose tolerance), fasting insulin and compromised insulin secretion (as assessed by increment in insulin to the increment in glucose over the first 30 min of an oral glucose tolerance test (delta I30/delta G30)) to predict future NIDDM. In the 8-year follow-up of the San Antonio Heart Study, NIDDM developed in 11.7% (107/914) of Mexican Americans and in 5.0% (18/362) of non-Hispanic whites (p < 0.001). Multivariate predictors of NIDDM by multiple logistic regression analysis included increased age, BMI, WHR, fasting insulin and impaired glucose tolerance and decreased insulin secretion. The strongest independent predictors of NIDDM were high fasting insulin and decreased insulin secretion. These risk factors predicted NIDDM equally well in high and low-risk populations.