As angiotensin-converting enzyme inhibition is accompanied by a marked decrease in glomerular protein loss, the hypothesis was tested that an increase of the glomerular transcapillary hydraulic pressure difference by exogenous angiotensin II would increase microalbuminuria in patients with insulin (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Acute effects of increasing doses of angiotensin II (1, 3 and 6 ng/kg/min) were studied on mean arterial pressure (MAP), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), filtration fraction (FF), total renal vascular resistance (TRVR), and urinary albumin excretion rate (UAER) in 11 IDDM and 11 NIDDM microalbuminuric patients. Angiotensin II infusion changed MAP from 100 +/- 3 mmHg at baseline to 105 +/- 3, 111 +/- 3, and 116 +/- 3 mmHg (P < 0.001), ERPF from 542 +/- 29 to 478 +/- 24, 429 +/- 23, and 382 +/- 19 ml/min (P < 0.001), FF from 20.2 +/- 0.06 to 23.1 +/- 0.7, 27.1 +/- 1.1, and 29.8 +/- 1.2% (P < 0.001), and TRVR from 9454 +/- 809 to 11,158 +/- 930, 13,310 +/- 1206, and 15,538 +/- 1362 dyne s cm-5 (P < 0.001). GFR and UAER, however, did not change significantly. Therefore, during angiotensin II infusion ERPF decreased, while FF and TRVR increased. As UAER and GFR remained unchanged, the presumed rise in intraglomerular capillary pressure by exogenous angiotensin II did not increase UAER. We suggest that during manipulation of the renin-angiotensin system, as in other renal diseases with proteinuria, factors other than glomerular transcapillary hydraulic pressure determine the degree of urinary albumin loss in microalbuminuric IDDM and NIDDM patients.