The effects of two histamine 2-receptor antagonists, cimetidine and ranitidine, on the single-dose pharmacokinetics of diltiazem were studied in 6 healthy subjects. A single 60-mg oral dose of diltiazem was administered alone, after ranitidine 150 mg twice daily for 7 days, and after cimetidine 300 mg 4 times a day for 7 days. Plasma samples were obtained over a 10-hour period and analyzed for the parent drug and one of its metabolites, deacetyldiltiazem (DAD). Concurrent cimetidine produced a significant (p less than 0.05) increase in diltiazem levels at most time points, in peak concentration and area under the concentration-time curve. These variables were also increased during concurrent ranitidine administration but did not reach statistical significance. The DAD plasma concentration was below measurable levels during the control phase but increased during concurrent cimetidine and ranitidine administration. Caution should be exercised when diltiazem is administered concurrently with cimetidine and possibly, ranitidine.