The present study was designed to test the hypothesis that the fetal autonomic nervous system modulates the fetal plasma atrial natriuretic factor and urine flow responses to vascular volume expansion. To do this, isotonic saline solution (2% of estimated body weight) was infused intravascularly over a 10-minute period into autonomically intact or autonomically blocked fetal sheep. The autonomically intact fetuses responded to the infusion with a significant rise in arterial and venous pressures (p less than 0.0001), and atrial natriuretic factor increased by 36 +/- 8 (SE) pg/ml (p less than 0.05). In the autonomically blocked fetuses, the arterial pressure rise was greater (7.5 +/- 1.3 vs 2.6 +/- 0.7 mm Hg), whereas the venous pressure rise was not different from that seen in the intact fetuses. Atrial natriuretic factor increased by 44 +/- 20 pg/ml (p less than 0.05) in the blocked fetuses. Urine flow increased by similar amounts in the two groups (maximal increase above control of 0.33 +/- 0.11 in the intact and 0.27 +/- 0.10 ml/min in the blocked fetuses). Thus autonomic blockade did not significantly alter either the atrial natriuretic factor, urine flow, or venous pressure responses to volume loading in the fetal sheep. Therefore it appears that the autonomic nervous system does not play a major role in modulating atrial natriuretic factor, urine flow, or venous pressure responses to acute vascular volume expansion in the late gestational fetal sheep.