Antipyrine metabolite kinetics have been characterized in rats receiving an intravenous infusion of either saline, cimetidine, or metyrapone. 14CO2 exhalation rate-time profiles following [N-methyl-14C] antipyrine administration demonstrate that, when either cimetidine or metyrapone is maintained at a steady state plasma concentration, a constant degree of inhibition is evident. Under the conditions imposed in this in vivo study, the inhibitory potency of metyrapone is approximately 6 times that observed with cimetidine. Rate constants for the formation of 4-hydroxy-, 3-hydroxymethyl-, and norantipyrine have been calculated using breath and urinary metabolite data under the steady state inhibitory states. Metyrapone nonselectively inhibits the formation of all three oxidative metabolites by approximately one-third. Cimetidine inhibition is selective where rates of 3-methyl-hydroxylation and N-demethylation are reduced by 50% yet 4-hydroxylation is unaffected. The value of assessing inhibitory responses under steady state conditions is discussed and the nonlinear nature of the kinetics of inhibition, when a single bolus dose of inhibitor is used, is illustrated by means of computer simulation.