The relationship between sulfamethazine disposition kinetics and acetylation phenotype was studied in man. Sulfamethazine pharmacokinetic parameters were determined after the administration of the drug as an oral suspension. When the half-life, acetylation rate constant, or per cent available dose excreted in the urine as acetylsulfamethazine of each subject was plotted on frequency distribution histograms, bimodal distribution patterns were observed. However, when acetylation clearance values were plotted in the same manner, an apparent trimodal pattern was seen. The failure to identify the presumed homozygous rapid acetylator using the commonly employed indices of drug metabolism, i.e., half-life, metabolic rate constant, or per cent of the dose metabolized, was attributed to a significant increase in the apparent volume of distribution of this genotype, as well as the low renal clearance of sulfamethazine found in all genotypes. This preliminary study points out the value of using metabolic clearance as an index of drug metabolizing capacity and suggests its application to further pharmacogenetic studies.