The influence of endogenous nitric oxide (NO) on prostaglandin biosynthesis in rat carrageenin oedema was studied. Oedema formation and prostaglandin E2 generation in the inflamed paw were both increased by L- but not D-arginine and reduced by the NO synthase inhibitor, L-NG-nitro arginine methyl ester, and the NO scavenger, haemoglobin. Methylene blue, an inhibitor of the soluble guanylate cyclase, had no effect. These results suggest that endogenous NO modulates carrageenin oedema by increasing prostaglandin biosynthesis at the inflammatory site through a cGMP-independent mechanism.