A series of 2-substituted 3,4-dimethylfuro[2,3-c]pyrazole- 5-carboxamides and related compounds have been synthesized and their antiallergic activities were evaluated. Most derivatives with a lower alkyl group at position 2 were orally active. Among them, N-ethyl-2,3,4-trimethylfuro[2,3-c]pyrazole- 5-carboxamide (III3),2-ethyl-N-methyl-3,4-dimethylfuro[2,3-c]pyrazole-5-ca rboxamide (III14), 2-isopropyl-N-methyl-3,4-dimethylfuro[2,3-c]pyrazole-5- carboxamide (III27),5-(4,5-dihydro-5-oxo-1,3,4-oxadiazol-2-yl)-2,3,4- trimethylfuro [2,3-c]pyrazole (IV1) and 5-(4,5-dihydro-5-oxo-1,3,4-oxadiazol-2-yl)-2-isopropyl-3,4- dimethylfuro[2,3-c]pyrazole (IV3) showed promising antiallergic effects. The structure-activity relation of these 3,4-dimethylfuro[2,3-c] pyrazole derivatives was examined. An amide or 5-oxo-1,3,4-oxadiazole substituent at position 5 was favorable, while introduction of a carboxylic acid or acrylic acid moiety was unfavorable. However, none of these compounds exerted a significant inhibitory effect on mast cell degranulation. Compound III27 and IV3 showed potent anti-allergic activity. We found that they also suppressed histamine-, serotonin-, bradykinin- and substance P-induced ear edema in mice. In compound 48/80-pretreated mice, the preformed mediators in mast cells in the ear were greatly reduced. Under this condition, the bradykinin- and substance P-induced ear edema was suppressed by compound III27 and IV3 to a significantly greater extent than by diphenhydramine combined with methylsergide. These results indicated that the antiallergic effect of 3,4-dimethylfuro[2,3-c]pyrazole derivatives probably involves protection of the vasculature against the effects of challenge by several mediators.