Cyclosporine A (CsA) causes vasoconstriction and decrease in glomerular filtration rate. Experiments were conducted in isolated glomeruli to study effects of CsA of glomerular perfusion and independent of systemic or renal factors. CsA caused a dose dependent decrease in glomerular volume consistent with mesangial contraction. The ultrafiltration coefficient Kf was significantly lower after incubation in 4 X 10(-4) M CsA when compared to control (2.81 +/- 0.2 vs 5.19 +/- 0.5 nl/min X mm Hg; p less than 0.001). Hydraulic conductivity Lp was diminished by CsA from 2.69 +/- 0.11 to 1.41 +/- 0.05 microliter/min X mm Hg X cm2 (p less than 0.001). These findings demonstrate a direct effect of CsA on the glomerulus which must be considered in addition to drug-induced changes in perfusion and tubular function.