The H2-antagonists famotidine and nizatidine produced a dose-dependent inhibition of histamine release from human colonic mucosal and muscle mast cells stimulated with anti-IgE. The IC30 values were in the range 0.5-10 microM and the maximum inhibition approached 50%. The compounds showed similar efficacy against rat peritoneal mast cells but were more potent. The cytoprotectant misoprostol had a striking effect on the human colonic mast cells, producing more than 50% inhibition at concentrations of 0.1-1 nM, but was much less active against the rat cells.