Previous studies of hospitalized and ambulatory patients have found a higher prevalence of Staphylococcus aureus nasal colonization in diabetic than nondiabetic subjects. We examined this association in a geographically based study among 551 residents of the San Luis Valley of Colorado and found no statistically significant increase in the relative risk of nasal S. aureus colonization in 188 non-insulin-dependent diabetic (NIDDM) versus 363 nondiabetic subjects (relative risk 1.3, 95% confidence limits 0.9-1.8). Adjustment for confounding by age, sex, ethnicity, county of residence, and frequency of hospitalizations or physician visits in the previous year did not affect the results. Among the diabetic subjects, S. aureus colonization was not associated with type of treatment for diabetes, level of glucose control, clinical duration of diabetes, or frequency of hospitalizations or physician visits in the previous year. In this population-based study, diabetes mellitus did not increase S. aureus nasal colonization, suggesting that factors other than diabetes mellitus may have caused the higher colonization rate found in previous clinic-based studies.