It has been suggested that the substantial rise in fetal plasma arginine vasopressin (AYP) during intrauterine hypoxia/asphyxia reflects decreases in PaO2and/or pHa; however, the components of these “stresses,” i.e. PO2, PCO2, and pH, have not been controlled. Recently, only modest increases in fetal AVP secretion were seen during hypoxia independent of changes in pH and PCO2. Since the independent effects of metabolic acidosis on fetal AVP secretion are unknown, we induced acute metabolic acidemia in fetal sheep at 137 ± 4 (mean ± SD) days gestation with 1 M NH4C1, while monitoring mean arterial pressure, heart rate, PaO2, PaCO2, pHa, plasma osmolality, and blood concentrations of electrolytes, AVP, dopamine, norepinephrine, and epinephrine. Mean arterial pressure, PaO2, PaCO2, and plasma osmolality and sodium were unchanged; pHa decreased from 7.37 ± 0.01 to 7.04 ± 0.05 (p<0.05) during NH4C1 and did not return to control levels until 24 h later. AVP increased from 2.85 ± 0.23 to 5.26 ± 1. 1 1 µU/ml (p<0.05) at the time of maximum acidosis, correlating with the fall in pHa (r=-0.67,p=0.001); however, after stopping NH4C1, AVP returned to baseline levels although pHa remained <7.15. In control studies using the same osmolar load, volume, and rate of infusion, AVP levels were unchanged. Only epinephrine was significantly (p<0.05) elevated during acidosis, but did not correlate with pHa or plasma AVP. Marked metabolic acidemia appears to have little or no effect on fetal AVP secretion, and fetal catecholamine secretion is variable. (Pediatr Res 21: 38-43,1987)