In this study, we prospectively evaluated the effect of oral cimetidine on serum lidocaine concentrations in 6 patients with suspected myocardial infarction. Compared to baseline lidocaine levels, total lidocaine concentrations increased by 8.2 +/- 7.8% at 6 hours, 16.4 +/- 9.0% at 12 hours and 27.9 +/- 9.4% at 24 hours after two doses of oral cimetidine. Unbound lidocaine concentrations increased by 14.3 +/- 4.1% at 6 hours, and 18.3 +/- 10.3% at 24 hours after cimetidine. In patients with myocardial infarction (3), total lidocaine concentrations increased by 24.2 +/- 10.4%, whereas unbound lidocaine increased by 8.9 +/- 10.2% at 24 hours. Therefore, increases in total lidocaine concentrations after cimetidine administration were considerably less than those previously reported and empiric dosage reductions of lidocaine in patients receiving cimetidine may not be appropriate.