Twenty renal transplant recipients (RTx) with a normal ultrasound pattern of renal artery who began angiotensin-converting enzyme inhibitor (ACEI) therapy within 14 months after surgery (ACEI(+)) were studied retrospectively to evaluate endogenous creatinine clearance/1.73 m(2) body surface area (CrCl), proteinuria (UP), UP/CrCl (FUP), mean arterial pressure (MBP), total cholesterol, LDL, HDL, and triglycerides. Before (T(0)) and every month for 2 years after initiation of ACEI. Twenty-four RTx who never received ACEI (ACEI(-)) were studied in the same fashion. No differences in the parameters were noted at T(0); all RTx had CrCl >60 mL/min, Up less than 0.5 g/d, and stable renal function for 3 months before the study. In the ACEI cohort CrCl was reduced after 2 years compared with T(0) (65.6 +/- 2.8 vs 76 +/- 3.2 mL/min, P <.004), UP and FUP were both increased (660 +/- 60 vs 130 +/- 20 mg/d, 8.9 +/- 1.3 vs 2.8 +/- 0.6 mg/mL x 10(3); P <.001 and.002, respectively). UP >0.5 g/d was present in three cases. After 2 years the ACEI(+) group showed a decrease in CrCl (68.2 +/- 3.1 vs 73 +/- 2.2 mL/min) and the increase in UP (181 +/- 21 vs 139 +/- 18 mg/d) and in FUP (3.1 +/- 0.7 vs 2.6 +/- 0.9 mg/mL x 10(3)), which were not significantly different from the values at T(0). No cases showed UP >0.5 g/d. Moreover UP (P <.04), FUP (P <.03) and the percent reduction of CrCl (11.2 +/- 2.5% vs 4.6 +/- 1.8%, P <.05) were greater among ACEI(-) than ACEI(+) patients at 2 years. ACEI(-) patients showed correlation between the percent reduction of CrCl and UP (r =.51, P <.04). The values of MBP and lipids did not reveal any significant difference between the two groups. In conclusion, this study suggests that ACEI have a renoprotective effect, when used early, and may also prevent chronic allograft nephropathy.