The effects of various inhibitors and anti-allergic drugs on histamine secretion from peritoneal mast cells of the rat, mouse and hamster have been compared. Phosphodiesterase inhibitors, cAMP analogues and beta-adrenoceptor agonists variously blocked release of the amine from all three cell types. The mouse cells were rather less sensitive to the former agents than those of the rat and hamster. Disodium cromoglycate inhibited histamine secretion from rat peritoneal mast cells, was less active against the hamster cells and completely ineffective against those of the mouse. Other chromones showed varied patterns of differential reactivity but phloretin and the flavonoid quercetin were essentially equiactive against all three cell types. The tetrazoles AH 9679 and doxantrazole prevented histamine release in each case but were significantly less active against the mouse cells. These results further emphasize the functional heterogeneity of mast cells from different sources.