The short term effects of the cardiac peptide, Atrial Natriuretic Factor(ANF) in the fetus are to increase vascular permeation of fluid and protein and to decrease blood volume. However chronic ANF-effects on the fetus are unknown. We measured blood volume (BV) using 99mTc labeled RBC's, extracellular fluid volume (ECF) as the inulin space, sodium excretion, GFR, heart weight, and heart weight expressed as a percentage of body weight, in 11 unanesthetized chronically instrumented late-gestation fetal sheep (127± 0.5 wks, mean ± SEM). Six fetuses received a continuous ANF infusion over a period of 5 days (131±10 ng/min). Five control fetuses received saline vehicle. ANF concentration increased from 70 ± 7 to 197± 18 pg/ml (p = 0.015) in the ANF group but was unchanged in the control group (70 ± 11 to 76 ± 5 pg/ml, NS). Boggy tissues and sizeable fluid collections in body cavities were observed in the ANF fetuses but not in the controls. Heart weight was lower in the ANF group compared to control (20.5± 2.3 vs 26.2 ± 2.1 g, p = 0.07). Body weight was not different, whereas heart weight expressed as a percentage of body weight was significantly decreased in the ANF group compared to controls (0.67± 0.03 vs 0.83 ± 0.02%, p = 0.029). The ECF/BV ratio significantly increased from 4.6 ± 0.3 to 5.7 ± 0.2 (p<0.005) in the ANF group whereas the ECF/BV ratio was unchanged in the control group. Sodium excretion increased significantly in the ANF group (16.4 ± 3.4 to 39.8 ± 11.2 μeq/min, p <0.05) but was unchanged in the control group (10.4 ± 5.4 to 13.6 ± 4.9). The glomerular filtration rate and the fractional excretion of sodium was unaffected. These data suggest that ANF plays a direct role in the development of fetal hydrops and has sustained effects on the fetal renal and cardiovascular systems. ANF decreases BV relative to ECF and appears to increase sodium excretion as well. ANF-induced alterations of BV-ECF balance may result in decreased cardiac filling that indirectly attenuates cardiac growth. Alternatively, a direct ANF-induced myocyte effect through cGMP-dependent protein kinase inhibition of cardiac growth signal transduction deserves further study.