cyclosporin A is a widely used immunosuppressant agent which has direct vascular effects such as contraction of the arterial smooth muscle and potentiation of other vasoconstrictor agents. In rabbit isolated arterial segments, the contractile effects of a cyclosporin A preparation (Sandimmun; 10(-6) M) and its solvent (Cremophor-EL) were investigated. Both caused an increase in the basal tension of arterial segments after an incubation period of 1 hour. Several substances were tested to antagonize the contractile activity of the cyclosporin A preparation and its solvent. Prednisolone and quinacrine (phospholipase A2 inhibitors), indomethacin (cyclooxygenase inhibitor), verapamil (calcium antagonist), phentolamine (alpha-adrenoceptor blocker), captopril (angiotensin-converting enzyme inhibitor) and prazosin (alpha 1-adrenoceptor-blocking agent) decreased the contractile responses to the cyclosporin A preparation and its solvent in a comparable manner. These findings indicate that the solvent of the cyclosporin A preparation is responsible for the contractile effect of this latter preparation and that this contractile activity cannot be explained by a single mechanism.