In 7 healthy subjects theophylline and antipyrine elimination were determined before and during a course of oral cimetidine in a dose of 1 g/day. Plasma clearance of theophylline was reduced from 71.2 +/- 10.1 ml/min to 56.0 +/- 18.5 ml/min and the plasma clearance of antipyrine from 53.7 +/- 14.2 ml/min to 48.1 +/- 11.7 ml/min. Elimination half-life of theophylline was prolonged from 5.1 +/- 1.6 to 8.1 +/- 1.4 h. All these changes were statistically significant. Volume of distribution of theophylline (31.7 +/- 8.4 L before and 39.2 +/- 5.6 L during cimetidine administration) and plasma binding of theophylline (44.7 +/- 3.8% before and 44.3 +/- 3.1% during cimetidine administration) were not significantly different. Similarly, volume of distribution of antipyrine (45.8 +/- 14.0 vs. 47.6 +/- 17.9) was not significantly affected by cimetidine administration. We conclude that cimetidine impairs the elimination of theophylline and antipyrine in healthy subjects.