We used differential solute clearances and a theoretical analysis of glomerular ultrafiltration and dextran sieving to characterize the hemodynamic response of nine healthy humans to infusion of isoncotic, 5% albumin in saline or saline vehicle alone. During albumin infusion (10.2 +/- 0.2 ml.kg-1.30 min-1) plasma volume increased by 18%, but oncotic pressure rose by only 0.8 mmHg. Despite the hypervolemia, renal blood flow (RBF) declined by 140 ml/min and glomerular filtration rate (GFR) declined by 16 ml/min during the infusion. RBF increased progressively postinfusion, exceeding baseline by 135 ml/min after 4 h; GFR was restored to baseline. Although oncotic pressure declined by 2 mmHg, a similar transient decline in GFR (-13 ml/min) was associated also with infusion of saline vehicle alone (9.4 +/- 0.3 ml.kg-1.30 min-1), which increased plasma volume by 9%. Sieving coefficients of dextrans (radius 32–42 A) were lowered during and after either infusion, a phenomenon that we compute to reflect a reduction in glomerular pore size. Assuming that the transcapillary hydraulic pressure difference was not lowered, we calculate that there was a simultaneous depression of the ultrafiltration coefficient (Kf) during volume expansion with saline and possibly also to a lesser extent with albumin. The hypofiltration during either infusion delayed the onset of a natriuretic response until the filtered sodium load was restored to baseline in the postinfusion period. We propose that the net effect of changes in intracapillary pressures and Kf during volume expanding infusions is to transiently lower GFR, thereby preventing the human kidney from mounting an immediate natriuretic response to acute hypervolemia.