Aminopyrine and caffeine metabolism was evaluated in vivo in 21 healthy volunteers in order to elucidate whether the acetylation capacity of the two substances correlates. The ratio of the aminopyrine metabolites 4-acetyl-aminoantipyrine (AAA)/4-aminoantipyrine (AA) was compared with the ratios of caffeine metabolites AAMU/1-X and AAMU/(AAMU + 1-X + 1-U). All the subjects phenotyped as slow acetylators with caffeine displayed AAA/AA ratios lower than 3.4, whereas the extensive acetylators had ratios higher than 3.8. Therefore, the acetylator phenotype determined with caffeine cosegre-gated with the capacity to acetylate the aminopyrine metabolite AA. The N-demethylation of aminopyrine and caffeine correlated strongly in the subjects studied (p < 0.001). A highly significant correlation (r = 0.92; p < 0.001) was also observed between caffeine N(l)- and N(7)-demethylation activities. In addition, most N-demethylation steps of both drugs significantly correlated, suggesting partial contributions by identical or closely related enzymes in their metabolism.