Twelve healthy habitual cigarette smokers and eight non-smokers participated in a double-blind placebo controlled study to determine the effect of smoking on the pharmacokinetics and pharmacodynamics of the H2-receptor antagonist famotidine. In smokers, cigarette smoking was standardised and started 1 h before (A), or 2 h after (B) drug administration, or was prohibited (C). Intragastric pH-levels (IGpH) were measured with an ambulatory pH-recorder. Famotidine (40 mg orally) significantly raised median 22 h IGpH in non-smokers and smokers in all study periods. The smoking sequence (A, B, C) did not significantly influence median 22 h IGpH in both placebo-treated and famotidine-treated smokers, and no significant difference in median 22 h IGpH was shown between smokers and non-smokers. Plasma drug concentrations were similar in the various experiments, although famotidine was detected earlier in plasma from non-smokers compared with smokers (P less than 0.05). Smoking did not interfere significantly with the pharmacokinetics and pharmacodynamics of famotidine.