Agonist-antagonist interactions at histamine receptors have been re-examined using improved techniques, on the mouse isolated, lumen-perfused, stomach gastric acid assay. Using histamine as agonist, pKB values have been estimated for burimamide, metiamide, cimetidine, ranitidine, oxmetidine and famotidine on both the gastric and guinea-pig isolated right atrium assays. With the exception of oxmetidine on the atrial assay, these compounds behaved as competitive antagonists on both assays. Oxmetidine significantly depressed basal rate on the atrial assay and the Schild plot slope parameter (0.81) was significantly less than one. The pKB values estimated on the gastric assay were lower than those on the atrial assay. However, the difference between the values on the gastric and atrial assays was not constant. The difference between the two assays for famotidine was not significant. We conclude that the apparent varying selectivity of the antagonists for gastric and atrial histamine H2-receptors may be explained by the differential loss of antagonists into the gastric secretion from the receptor compartment and that there is no need to postulate heterogeneity of histamine H2-receptors.