We attempted to determine whether pregnancy alters the vasodepressor response to both physiologic and pharmacologic infusions of atrial natriuretic factor 99-126. Ten virgin and 10 pregnant (17 +/- 1 days of gestation) conscious, unrestrained Sprague-Dawley rats with chronic indwelling vascular catheters were studied. Mean arterial pressure and heart rate were measured in response to steady-state infusions of either saline solution or increasing concentrations of atrial natriuretic factor (range 5 to 2560 ng.kg-1.min-1). Basal mean arterial pressure was significantly lower in pregnant rats than in virgin rats (89 +/- 3 vs 97 +/- 2 mm Hg, p < 0.02). Atrial natriuretic factor induced significant dose-dependent decreases in mean arterial pressure and heart rate in virgin and pregnant rats (p < 0.001). The hypotensive effects of atrial natriuretic factor were blunted in the pregnant rats only in response to the highest concentrations of atrial natriuretic factor administered (-27 +/- 3 mm Hg in pregnant rats vs -43 +/- 3 mm Hg in virgin rats, p < 0.005). The vasodepressor response to physiologic infusions of atrial natriuretic factor was not affected by pregnancy status. However, pharmacologic infusions of atrial natriuretic factor resulted in a blunted vasodepressor response in the pregnant animals. This may be due to alterations in vascular atrial natriuretic factor receptors, changes in the clearance rate of atrial natriuretic factor, or the modulating effects of other vasoactive hormones.