BACKGROUND Cyclosporin (CsA) is a potent immunosuppressive drug whose main side-effect is nephrotoxicity. In the kidney, CsA induces vasoconstriction with a decrease in renal blood flow (RBF) and glomerular filtration rate (GFR) and a significant increase in renal vascular resistance (RVR). CsA enhances platelet-activating factor (PAF) synthesis in mesangial cells in vitro. PAF, a secondary mediator of anaphylaxis and inflammation, exhibits vasoactive properties in the kidney similar to those of CsA. METHODS The in situ autoperfused rat kidney model was used to investigate whether PAF plays a role in the haemodynamic injury induced by CsA. RESULTS In this model, CsA (40 mg/kg and 20 mg/kg i.v.) induced a significant decrease in RBF and in GFR and an increase in RVR. BN 52021, a potent and specific PAF antagonist (20 mg/kg i.v. bolus dose) induced a significant increase in GFR (137 +/- 32% of initial value, P < 0.05). BN 52021 (20 and 10 mg/kg) also significantly prevented the decline in RBF and GFR induced by CsA. CONCLUSIONS We have demonstrated that the PAF antagonist BN 52021 can minimize the alteration of renal function induced by CsA.