The renal side effects are the major limitation of the use of cyclosporine in clinical transplantation. We studied the reversibility of changes in renal hemodynamics and glomerular barrier function in 17 patients with moderately impaired renal function at least 1 year after kidney transplantation. All patients were studied both during cyclosporine treatment and 3 months after conversion to azathioprine. During azathioprine treatment both glomerular filtration rate and effective renal plasma flow increased significantly (from 44.3 +/- 4.2 mL/min to 63.5 +/- 5.4 mL/min and from 192 +/- 12.8 mL/min to 260 +/- 14.6 mL/min, respectively). Despite the marked changes in renal hemodynamics, no significant changes were observed in the fractional clearances of uncharged dextrans. When calculating the characteristics of the filtration barrier, we observed a trend toward an increase in the ultrafiltration coefficient (Kt). This trend was abolished when an increase in net filtration pressure (delta P) was assumed to result from reduced prerenal vasoconstriction. We conclude that despite marked improvement of renal perfusion and glomerular filtration, conversion from cyclosporine to azathioprine did not significantly alter the permeability characteristics of the glomerular filtration barrier in renal transplant recipients with moderately reduced renal function. Improvement in renal function following conversion could result from an increase in either Kf or delta P. Since renal plasma flow was increased significantly, the observed improvement in glomerular filtration rate is likely to be, at least in part, due to an increase in glomerular capillary plasma flow.