Plasma antipyrine half-lives exhibited an inverse relationship to hepatic microsomal aniline hydroxylase (r = –0.78) and ethylmorphine N-demethylase (r = –0.79) activities in healthy mongrel dogs. However, no close correlation occurred between plasma antipyrine half-life and hepatic microsomal cytochrome P-450 content (r = –0.07) cytochrome c reductase activity (r = –0.21) or NADPH oxidase activity (r = –0.30). In dogs retested at 21 days, plasma antipyrine half-life was a highly reproducible value in each animal. However, at shorter time intervals the dose of antipyrine used (75 mg/kg, i.v.) probably induced hepatic microsomal drug metabolism since retesting 10 days after the initial dose disclosed shortening of the plasma antipyrine half-life in each animal. These experiments suggest that under certain conditions plasma antipyrine half-lives may be useful indices of rates of hepatic metabolism of several compounds chemically unrelated to antipyrine.