Hypertension and renal mass reduction induce glomerular hypertension (GH), hyperfiltration (HF) and renal injury. GH may contribute to allograft loss in post-transplant hypertensive patients (PT x HT). HF and GH may be evaluated by renal response to acute protein intake (API). Since ACE inhibition may prevent GH, the effects of fosinopril (Fos) were evaluated in 10 PT X HT on azathioprine and prednisone. Patients received 5 to 40 mg/day of Fos during 12 months. Baseline MAP (111.1 +/- 2.9 mm Hg) was significantly reduced by 10 to 12 mm Hg, rising to 114.7 +/- 2.7 mm Hg after Fos was administered. GFR (63.7 +/- 5.9 ml/min) decreased after 4 (48.1 +/- 4.6, P less than 0.05) and 12 months (50.7 +/- 4.6, P less than 0.05), rising to 59.4 +/- 5.6 after Fos was given. There was no GFR response to API before and after one month of Fos, however, a clear response became apparent at 4 (+ 27% P less than 0.05), and 12 months (+ 18%, P less than 0.05), disappearing after Fos discontinuation. Proteinuria (918.8 +/- 710.6 mg/d) decreased after 4 (72.3 +/- 21.6 mg/d, P less than 0.05) and 12 months, rising to 297.8 +/- 172.3 mg/day after therapy. GFR response to API in 22 controls and 17 uninephrectomized donors was 13 and 11%, respectively. Lack of response to API in PT x HT suggests HF and GH. Reduction of GFR, restoration of response to API and reduction of proteinuria, indicate that ACE inhibition with fosinopril ameliorates HF and GH. This effect may be beneficial in preventing hemodynamic-mediated allograft injury.