The importance of the temporal relationship between meal and nizatidine intake was studied in a six-armed, double-blind, placebo-controlled trial. Eleven healthy volunteers received early (18.00 hours) or late (21.00 hours) supper, with either placebo, early (18.00 hours) nizatidine, or late (21.00 hours) 300 mg nizatidine. Ambulatory 21-hour gastric pH-metry was performed and plasma nizatidine concentrations were determined by high pressure liquid chromatography. Early-nizatidine/early-supper (median pH 2.50), but not late-nizatidine/late supper (median pH 2.30), produced significantly higher median 21-hour pH values than did early-nizatidine/late-supper (median pH 1.90). Concomitant food delayed the absorption of nizatidine but did not change the drug's bioavailability. Oral nizatidine should be taken with food, preferably early in the evening, to optimize its anti-secretory effect.