The effect of timing of cyclosporine administration on functional recovery from renal ischemia was studied in Sprague-Dawley rats. Animals were given cyclosporine and subjected to renal ischemia by temporarily occluding both the renal artery and vein. Our data demonstrate no significant difference in serum creatinine among rats subjected to renal ischemia, cyclosporine, or cyclosporine-vehicle cremophor EL administration, or the control group. On the other hand, renal ischemia in combination with cyclosporine resulted in rapid and marked deterioration in renal function with serum creatinine peaking on Day 2. The most significant rise was in rats that received cyclosporine 4 hr prior to induction of renal ischemia (4.7 +/- 0.5 mg/dl), followed by those that received cyclosporine 4 and 24 hr postischemia (2.8 +/- 0.5 and 3.2 +/- 0.7 mg/dl, respectively). Cyclosporine administration 24 hr prior to renal ischemia resulted in the least elevation of the serum creatinine (2.1 +/- 0.5 mg/dl) and the earliest return to the baseline value. Our data suggest that the timing of cyclosporine administration in rats subjected to renal ischemia influences the extent of renal injury and the subsequent recovery of renal function.