We measured the effects of cimetidine on antibiotic concentrations in the luminal portion of gastric mucosa. Guinea pigs were premedicated with cimetidine 4 mg/kg intramuscularly. Clindamycin, an antibiotic previously characterized under physiologic pH conditions, was administered intramuscularly and levels measured in serum and tissue using a high-pressure liquid chromatography (HPLC) technique. The luminal mucosa concentration of clindamycin at 1 hr (pH 5.9) was fivefold greater compared to the concentrations seen under physiologic (pH 2.0) conditions (81.5 micrograms/g vs 15.9 micrograms/g; P less than 0.05) and 10-fold greater at 2 hr (82.7 micrograms/g vs 8.09 micrograms/g; P less than 0.05). There was no difference in peak serum levels between the groups. The finding that an antibiotic with characteristics of a base is thus affected by a nonconservative acid inhibitor such as cimetidine supports the presence of an acidic storage pool as proposed by other investigators. H2-receptor antagonists may be useful therapeutic adjuncts in H. pylori infections by virtue of increasing gastric concentrations of antibiotics that behave as weak bases.