Hyperfiltration precedes renal function loss in several nephropathies. Animal studies suggest this may be due to accompanying increases in transglomerular capillary hydrostatic pressure difference (delta P) and/or altered glomerular processing of macromolecules. Renal hemodynamics increase strikingly in human pregnancy. To test the hypothesis that these alterations are not potentially harmful, clearances of inulin, p-aminohippurate, and neutral dextrans were measured at 16- and 36-wk gestation, then 4 mo postpartum, in 11 normotensive women. Results were analyzed using two computer modeling programs. Glomerular filtration rate and renal plasma flow (RPF) were markedly elevated in early and late pregnancy (135 +/- 6 and 895 +/- 53 and 135 +/- 6 and 754 +/- 32 ml/min, respectively, vs. 87 +/- 7 and 520 +/- 17 ml/min postpartum). Gestational hyperfiltration was primarily due to RPF increments with a minor contribution from decrements in capillary oncotic pressure. Fractional dextran clearances (particularly the smaller dextrans, 30-39 A radii) were lower in early pregnancy, decreasing further in late pregnancy. There was no evidence of increased delta P and alterations in glomerular membrane porosity resolved postpartum. These data provide a database by which to study effects of pregnancy on chronic renal disease.