The role of nitric oxide (NO) on aloe-induced diarrhoea was studied in the rat. Nine hours after oral administration, aloe produced diarrhoea at doses of 5 g kg(-1)(20% rats with diarrhoea) and 20 g kg(-1) (100% of rats with diarrhoea). Lower doses of aloe (0.1 and 1 g kg(-1) did not produce a diarrhoeal response. Pre-treatment (i.p.) of rats with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME 2.5-25 mg kg(-1) reduced the diarrhoea induced by aloe (20 g kg(-1) 9 h after its oral administration. L-NAME (25 mg kg(-1)) also reduced the increase in faecal water excretion produced by aloe (20 g kg(-1). L-arginine (1500 mg kg(-1), i.p.), administered to rats pre-treated with L-NAME (25 mg kg(-1), drastically reduced the effect of L-NAME on diarrhoea and increase in faecal water excretion induced by aloe (20 g kg(-1). Given alone, L-arginine did not modify aloe-induced diarrhoea. Basal Ca2+ -dependent NO synthase activity in the rat colon was dose-dependently inhibited by aloe (0.1-20 g kg(-1)) and by aloin (0.1-1 g kg(-1)), the active ingredient of aloe. These results suggest that endogenous NO modulates the diarrhoeal effect of aloe.