The following study was performed to determine whether calcium channel blockers, delivered before or after an ischemic insult, were effective at reducing cyclosporine-induced exacerbation of renal ischemic injury. When cyclosporine (5 mg/kg) was administered intravenously to rats after 30 min of renal ischemia, GFR fell by 60% compared with values observed in rats subjected to ischemia alone (190 +/- 30 vs. 330 +/- 40 microliters/min/100 g; P less than 0.05). Pretreatment with verapamil (10 micrograms/kg/min delivered intravenously) prevented the fall in GFR (320 +/- 70 microliters/min 100 g), as did pretreatment with nitrendipine, 1 micrograms/kg/min (460 +/- 90 microliters/min/100 g). Verapamil was less effective if given after the ischemia-cyclosporine insult (GFR 260 +/- 90 microliters/min/100 g), and nitrendipine given at this time had no beneficial effect at all (GFR 180 +/- 10 microliters/min/100 g). The doses of calcium channel blockers used had no protective effect on renal ischemic injury alone. Blood pressure during study ranged between 105 and 119 mm Hg with minor differences between groups. Sodium and potassium excretion and urinary flow rates were similar in all groups, except for a slight increase in sodium excretion in verapamil-treated rats. These values demonstrate that calcium channel blockers ameliorate the exacerbation or renal ischemic injury induced by cyclosporine if given before but not after the ischemia-cyclosporine insult. The protective effect of these agents, used preischemia in cyclosporine-treated rats, is observed with intravenous use of the drugs at doses that have no protective effect on renal ischemic injury alone.