Gastric juice pH, bacterial flora, and the H2 breath excretion were studied in patients treated with 150 mg ranitidine twice daily. The intragastric pH and bacterial contents rose during therapy. Before treatment upper respiratory tract bacteria were found in 4 of 23 patients and after 4 weeks of medication in 15 of 23. The median bacterial concentration was increased (p less than 0.01) and in five patients included bacteria normally found in the colon. Prolonged therapy for up to 12 weeks (n = 8) did not further change the bacteriologic pattern. Prophylactic treatment for 1 year (n = 3) showed gastric bacteria in high concentration, including Pseudomonas, in one patient. Postprandial H2 production remained unchanged after 4 (n = 23) and 12 (n = 7) weeks of therapy. In two of three patients treated prophylactically H2 excretion was increased after 1 year of medication. We conclude that acid reduction with ranitidine causes changes of the intragastric bacterial flora similar to those with other acid-reducing drugs in equipotent doses. The unchanged H2 breath test result after 4 and 12 weeks of treatment contradicts small-intestinal bacterial overgrowth. The elevated H2 excretion in two of the three patients after 1 year of treatment suggests the importance of a time factor in small-intestinal bacterial colonization.