Pregnancy in healthy women is associated with increments in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). We hypothesized that the hyperfiltration of normal pregnancy attenuates or exhausts renal reserve. In 21 healthy females studied serially in early and late pregnancy and then on average 15 wk postpartum, GFR and ERPF were determined by inulin and p-aminohippurate clearances, respectively, before and during either an amino acid infusion (Vamin 9; Kabi Pharmacia) (n = 14) or a control infusion of Hartman's solution (n = 7), both infused at 4 ml/min for 210 min. In early and late pregnancy, GFR increased significantly in response to amino acid infusion [from 137 +/- 29 to 162 +/- 35 ml/min (P < 0.001) and from 134 +/- 29 to 148 +/- 40 ml/min (P < 0.01), respectively], with the increments (18 and 10%, respectively) not significantly different from postpartum (non-pregnant) when GFR increased by 12% from 94 +/- 22 to 105 +/- 23 ml/min (P < 0.002). Amino acid infusion significantly increased ERPF from 874 +/- 188 to 980 +/- 215 ml/min in early pregnancy (P < 0.01), from 684 +/- 135 to 773 +/- 181 ml/min in late pregnancy (P < 0.01), and from 507 +/- 121 to 560 +/- 141 ml/min postpartum (P < 0.006), increments of 12, 13, and 10%, respectively. GFR did not change in response to control infusion. We conclude that, despite gestational increments in renal hemodynamics of > 40%, pregnancy does not attenuate the renal response to amino acid infusion.