Cyclosporin A (CsA) is a cyclic undecapeptide that has been used extensively as an immunosuppressive drug in transplantation medicine and is known to interact with L-arginine dependent pathways. We studied the in vitro and in vivo effects of CsA on nitric oxide synthase (NOS) activity in the rat kidney. CsA in concentrations of 44-2200 nM in vitro, and 12.5 or 25 mg/kg body weight per 4 weeks treated rat kidneys in vivo, significantly stimulated NOS activity. CsA may alter the Ca2+/Cam-dependent NOS activity by interacting with rat kidney Ca2+/calmodulin dependent events.