Abstract:The effect of three histamine H2-antagonists, cimetidine, ranitidine, and loxtidine, on acute rat paw oedema induced by histamine, carrageenan or complete Freund’s adjuvant, have been examined. Administered intraperitoneally, all three antagonists inhibited histamine-induced paw oedema dose-dependently in the range 0·5–15 μmol kg−1. The highest dose of cimetidine produced an inhibition of 92% as against 38% with the same dose of mepyramine. Analysis of the concentration-effect curves produced IC50 values of 1·66, 5·12 and 12·30 μmol kg−1 for cimetidine, loxtidine, and ranitidine, respectively, on histamine-induced oedema. In carrageenan-induced inflammation 12·3 μmol kg−1 of each of the three drugs produced significant inhibition, whereas in adjuvant-induced inflammation, (acute phase), cimetidine was very active, loxtidine less so and ranitidine inactive. Thus the relative effectiveness of the antagonists (cimetidine > loxitidine > ranitidine) appears to differ from their known potency relationship (loxtidine > ranitidine > cimetidine) on H2-mediated effects. We conclude that H2-receptors are involved in the induction of rat paw oedema, especially those induced by histamine and carrageenan, but that their relative effectiveness appears atypical.