Injection of zymosan-activated plasma into the rat paw induced oedema formation. Subplantar injection of the non isoform- selective inhibitors of nitric oxide (NO) synthase, N(G)-nitro-L-Arginine methyl ester and N(G)-methyl-L-Arginine, and of a scavenger of NO, haemoglobin, inhibited the early phase of oedema development. Inhibition of cyclooxygenase activity by indomethacin reduced the late increase in paw volume after the injection of zymosan-activated plasma. Methylene blue, an inhibitor of the soluble guanylate cyclase, had no effect. Our results suggest that in paw oedema induced by zymosan-activated plasma, the inflammatory response is dependent on NO (for the early phase) and prostaglandins (for the late phase). The effect of NO is likely to be mediated by a pathway which does not involve cyclic GMP.