Abstract--To test the hypothesis that normal volume expansion during pregnancy is impaired during chronic renal failure, we evaluated the effects of 5/6 nephrectomy (Nx) in Sprague-Dawley rats. Partial Nx was produced by ligation of 2/3 renal arteries and contralateral Nx. Control rats had a sham operation. Four weeks later, rats were assigned to nonpregnant (n=6/each) or pregnant groups (n=11 to 12/each). At day 21, blood pressure, plasma volume, renal function, hormonal levels, and reproductive outcome were determined. Statistical analysis was performed by ANOVA, and values were expressed as mean±SEM. Rats with 5/6 Nx had proteinuria and lower creatinine clearance; pregnancy did not affect these parameters. Blood pressure increased in 5/6 Nx rats and was reduced by pregnancy. Both pregnant groups had lower hematocrit and higher plasma volume values (nonpregnant control, 13.4±0.2; nonpregnant 5/6 Nx, 14.4±0.2; pregnant control, 19.1±0.7, pregnant 5/6 Nx, 19±0.9 mL, P<0.001). Pregnancy increased plasma renin activity only in control rats (nonpregnant control, 2.0±0.7; nonpregnant 5/6 Nx, 1.6±1.1; pregnant control, 36.1±7.9, pregnant 5/6 Nx, 6.1±1.8 ng AI/mL per hour, P<0.001). Serum aldosterone levels were unaffected by 5/6 Nx and were higher in pregnant than in nonpregnant rats. Urinary kallikrein activity was reduced by 5/6 Nx and not changed by pregnancy (nonpregnant control, 1499±237; nonpregnant 5/6 Nx, 346±90; pregnant control, 1595±180, pregnant 5/6 Nx, 374±95 nmol/16 hours, P<0.001). No significant differences in fetal and placental weights were observed between control and 5/6 Nx rats. Present data indicate that 5/6 Nx pregnant rats were able to normally expand plasma volume despite lower renin and kallikrein levels.