ABSTRACT. It has been suggested that the substantial rise in fetal plasma arginine vasopressin (AVP) during intrauterine hypoxia/asphyxia reflects decreases in P a 0 2 and/or pHa; however, the components of these "stresses," i.e. PO2, PC02, and pH, have not been controlled. Recently, only modest increases in fetal AVP secretion were seen during hypoxia independent of changes in pH and PC02. Since the independent effects of metabolic acidosis on fetal AVP secretion are unknown, we induced acute metabolic acidemia in fetal sheep at 137 f 4 (mean f SD) days gestation with 1 M NH4CI, while monitoring mean arterial pressure, heart rate, Pa02, PaC02, pHa, plasma osmolality, and blood concentrations of electrolytes, AVP, dopamine, norepinephrine, and epinephrine. Mean arterial pressure, Pa02, PaC02, and plasma osmolality and sodium were unchanged; pHa decreased from 7.37 f 0.01 to 7.04 f 0.05 (p < 0.05) during NH4CI and did not return to control levels until 24 h later. AVP increased from 2.85 f 0.23 to 5.26 f 1.11 ~U / m l (p < 0.05) at the time of maximum acidosis, correlating with the fall in pHa (r = -0.67, p = 0.001); however, after stopping NH4CI, 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) Abbreviations AVP, arginine vasopressin DA, dopamine NE, norepinephrine E, epinephrine MAP, mean arterial pressure HR, heart rate ANOVA, analysis of variance plasma of human infants (2-5) and shown to reflect not only the route and "stresses" of delivery, but also the occurrence of additional intrauterine "stresses" (2, 5,6). Furthermore, elevated plasma levels of AVP are seen in fetal sheep during hemorrhage (7-9) and hypoxia/asphyxia (10)(11)(12)(13)(14). Thus it appears that, as in the adult, AVP may be considered a "stress" hormone in the fetus.Whereas the stimulus for fetal hypersecretion of AVP during hemorrhage is clear, i.e. hypovolemia and baroreceptor mechanisms (9), the mechanisms(s) responsible for fetal AVP release during hypoxia/asphyxia is less clear. For example, although it has been suggested that during hypoxic insults (1 1, 13, 15) and parturition (14) the fall in PO2 is responsible for the elevated plasma levels of AVP, neither pH nor PC02 were controlled. Recently, we (12) reported that during mild to moderate fetal hypoxemia (a fall in Pa02 from 20 to 1 1 mm Hg) in the absence of alterations in either pHa or PaC02, plasma AVP levels rose from 2 to 10 pU/ml (2.5 pg/ml = 1.0 pU/ml) in contrast to the substantially greater increases reported by others and the nearly 200-fold rise observed during asphyxia, i.e. in the presence of hypoxemia, hypercapnia and acidosis (12). Moreover, we observed that maximum AVP le...