Following the investigation of debrisoquine (D) metabolism to 4-hydroxydebrisoquine (4OHD) in two populations, problems with the current practice of assessing this capacity by urinary D:4OHD ratios presented themselves. The distributions of both components of this ratio, when examined separately, clearly displayed interethnic differences. The mean 0- to 8-hr recovery of 4OHD in the Caucasian group was 15.5 +/- 1.1% (SE) of a 20-mg dose and 8.0 +/- 1.5% in the Oriental group. The corresponding values for unchanged D excretion were 33.0 +/- 4.1% in Orientals and 18.2 +/- 2.3% in Caucasians, a difference that is overlooked when D:4OHD ratios alone are examined. Although D and 4OHD excretion rates were equally variable, they correlated poorly; that is, they tended to vary independently of each other. This finding, in conjunction with the two separate ethnic differences, indicates that the ratio D:4OHD does not solely reflect an individual's capacity towards D 4-hydroxylation, and that equating these is unwarranted. This limitation does not necessarily invalidate judicious use of the ratio at the edges of the distribution curve, but it does call for additional investigations into the means to assess D metabolizing capacity in most subjects.