Nitric oxide (NO) biosynthesis increases during pregnancy and has been shown to suppress baroreceptor activity. The renal response to a simulated increase in circulating blood volume (atrial distension) is also attenuated at this time. We hypothesized that blocking NO biosynthesis during pregnancy would restore the renal response. Female rats were implanted with indwelling intracardiac balloons and central venous cannulas. After recovery, they were mated, and on day 14 of pregnancy, osmotic minipumps containing the NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) or its inactive enantiomer N^G-nitro-D-arginine methyl ester (D-NAME) (120 mg/2 ml at 10 µg/min) were implanted. In response to atrial distension (1 h), urine output increased in the D- and L-NAME-treated virgin rats. During pregnancy (day 20), this response was attenuated in the D-NAME-treated, but not the L-NAME-treated, animals, i.e., after a simulated increase in circulating blood volume, inhibition of NO biosynthesis restored the renal response of pregnant rats to that seen in virgin animals. We conclude that, during normal pregnancy, increased NO biosynthesis blunts the reflex renal response to atrial distension.