In a placebo-controlled, double-blind, multiple crossover study, the initial and chronic acid-inhibitory effect of lansoprazole 30 mg, orally administered half an hour before breakfast or immediately after breakfast, and of omeprazole 20 mg, administered postprandially, respectively, was investigated in 16 healthy volunteers, using ambulant 24-hr intragastric pH monitoring. On the first day of medication, only preprandially administered lansoprazole reduced acid secretion significantly (median 24-hr pH 3.0; P < 0.05). On day 15, the median 24-hr intragastric pH of lansoprazole preprandial (pH 4.1), lansoprazole postprandial (pH 4.3), and omeprazole postprandial (pH 3.3), respectively, differed significantly (P < 0.05) from placebo (pH 1.2). It is concluded that the interaction between food intake and lansoprazole administration only is important at the start of oral therapy. Lansoprazole taken before breakfast is effective even on the initial day of treatment.