The effects in man of liver disease, renal failure and hepatic microsomal enzyme induction on the elimination kinetics of antipyrine in saliva have been examined. Antipyrine (10 mg/kg) was given orally and assayed in saliva by gas-liquid chromatography. The mean antipyrine half-life from saliva in nine epileptic subjects receiving long term anticonvulsant drug therapy (6 hr +/- 0-9 SEM) was significantly shorter than in twenty normal healthy volunteers (10-7 +/- 0-6). Therapy included phenytoin and phenobarbitone, two drugs known to induce hepatic microsomal enzymes. Five subjects with chronic renal failure exhibited no significant difference in salivary anti-pyrine half-life (11-7 +/- 1-9) compared to the control group, whereas six subjects with chronic liver disease and impaired hepatic function had significantly increased half-life values (42-4 +/- 10). The results suggest that differences in the activity of hepatic microsomal enzymes are reflected by changes in salivary antipyrine elimination kinetics. Chronic renal failure appeared to have no effect on the function of these enzymes.