The role of nitric oxide (NO) in the reverse passive Arthus reaction elicited in the rat skin has been studied. The reverse passive Arthus reaction was modulated by test compounds given by intradermal injection in combination with anti-bovine serum albumin antibody. L-arginine (1.5-15 micromol/site) and the NO donor [1-hydroxy-2-oxo-3,3-bis (3-amonoethyl)- 1-triazenel (NOC-18; 1-10 micromol/site) both significantly reduced neutrophil infiltration and increased plasma leakage. The NO scavenger haemoglobin (30 and 100 micromol/site) did not affect oedema formation but increased neutrophil infiltration and attenuated the effects of L-arginine. The non-selective nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl ester (0.3-100 nmol/site) and N(G)-monomethyl-L-arginine (0.3-100 nmol/site) or the relatively selective inhibitors of the inducible NO synthase aminoguanidine (30-1000 nmol/site) and S-methylthiourea (3-1000 nmol/site) significantly reduced plasma leakage when given at high doses. Furthermore all these inhibitors exhibited a dose-related biphasic effect on neutrophil infiltration which was significantly increased by low doses and reduced by high doses, while intermediate doses had no effect. Phenylpropanolamine, a sympathomimetic vasoconstrictor (15-60 micromol/site), dose-dependently reduced both oedema formation and neutrophil infiltration. These results provide evidence for a relevant role of NO as a modulator of rat dermal reverse passive Arthus reaction and suggest that at the vascular level NO controls primarily the interaction between leucocyte and endothelial cell rather than the vascular permeability.