The recommended albumin (microg)/creatinine (mg) ratio (ACR) (30 microg/mg) to detect microalbuminuria does not account for sex or racial differences in creatinine excretion. In a nationally representative sample of subjects, the distribution of urine albumin and creatinine concentrations was examined by using one ACR value (> or =30 microg/mg) and sex-specific cutpoints (> or =17 microg/mg in men and > or =25 microg/mg in women) measured in spot urine specimens. Mean urine albumin concentrations were not significantly different between men and women, but urine creatinine concentrations were significantly higher (P < 0.0001). Compared with non-Hispanic whites, urine creatinine concentrations were significantly higher in non-Hispanic blacks (NHB) and Mexican Americans, whereas urine albumin concentrations were significantly higher in NHB (P < 0.0001) but not Mexican Americans. When a single ACR is used, the prevalence of microalbuminuria was significantly lower among the men compared with women (6.0 versus 9.2%; P < 0.0001) and among non-Hispanic whites compared with NHB (7.2 versus 10.2%; P < 0.0001). No significant difference in the prevalence of microalbuminuria between men and women was noted when sex-specific ACR cutpoints were used. In the multivariate adjusted model, female sex (odds ratio, 1.62; 95% confidence interval, 1.29 to 2.05) and NHB race/ethnicity (odds ratio, 1.34; 95% confidence interval, 1.12 to 1.61) were independently associated with microalbuminuria when a single ACR threshold was used. When a sex-specific ACR was used, NHB race/ethnicity remained significantly associated with microalbuminuria but sex did not. The use of one ACR value to define microalbuminuria may underestimate microalbuminuria in subjects with higher muscle mass (men) and possibly members of certain racial/ethnic groups.