The San Luis Valley Diabetes Study was undertaken to determine the prevalence, risk factors, and complications of non-insulin-dependent diabetes mellitus in Hispanics and Anglos (non-Hispanic whites), using a geographically based case-control design. The study was conducted in two southern Colorado counties that include 43.6% Hispanic and 54.9% Anglo persons. Medical practice records were reviewed to identify medically diagnosed diabetics. Controls without diabetes were identified by a two-stage random sample of households. Diabetics (n = 343) and controls (n = 607) attended a clinic where an oral glucose tolerance test or current hypoglycemic therapy confirmed or diagnosed non-insulin-dependent diabetes mellitus. The age-adjusted prevalence of confirmed non-insulin-dependent diabetes mellitus was 21/1,000 in Anglo males and 44/1,000 in Hispanic males, accounting for non-response. For Anglo females, the prevalence was 13/1,000 compared with 62/1,000 for Hispanic females, accounting for nonresponse. Previously undiagnosed non-insulin-dependent diabetes mellitus was also higher among Hispanics. There was a 2.1-fold excess of confirmed non-insulin-dependent diabetes mellitus among Hispanic males and a 4.8-fold excess among Hispanic females, consistent with the excess non-insulin-dependent diabetes mellitus among Hispanics reported from comparable studies. Non-insulin-dependent diabetes mellitus is a major chronic disease problem for persons of Hispanic ethnicity.