Nitro-L-arginine methyl ester (0.15 mumol/paw) significantly reduced both bradykinin- and 5-hydroxytryptamine-induced rat paw oedema. At this dose, L-arginine (L-Arg), D-Arg and nitro-D-arginine methyl ester had no effect on the oedematogenic responses induced by these agents. Nitro-L-arginine methyl ester, nitro-D-arginine methyl ester, L-Arg, D-Arg, L-arginine methyl ester and L-arginine ethyl ester, at the dose of 15 mumol/paw, significantly potentiated both bradykinin- and 5-hydroxytryptamine-induced oedema. This potentiation was not observed in animals treated with both mepyramine and methysergide or in animals chronically treated with compound 48/80. Nitro-L-arginine methyl ester (0.3-3 mM) and L-Arg (0.3-3 mM) released small amounts (< 10%) of histamine from rat peritoneal mast cells when compared to compound 48/80-induced degranulation (> 40%). Histamine release was quantified by radioimmunoassay since nitro-L-arginine methyl ester and L-Arg interfere with the fluorometric assay. The potentiation of paw oedema observed with higher doses of all arginine analogues is caused by in vivo mast cell degranulation and is probably due to the cationic charge of these substances.