In ovine and human pregnancy, fetal swallowing contributes importantly to amniotic fluid homeostasis. Fetal dipsogenic responsiveness to short-term plasma hyperosmolality develops in late gestation, although fetal swallowing is not stimulated in response to long-term plasma osmolality increases (2 to 3%), which typically stimulate adult drinking behavior. To explore the near-term fetal plasma osmolality threshold for swallowing stimulation, we examined the effects of i.v. hypertonic saline-induced subacute increases in plasma hypertonicity on fetal swallowing behavior. Central sites of activation were examined by c-fos expression in putative dipsogenic nuclei. The results demonstrate that subacute 2 to 3% plasma osmolality increases do not stimulate near-term ovine fetal swallowing. However, fetal swallowing activity significantly increased (3 times) after plasma osmolality increased Ͼ6% above basal values. Consistent with a specific dipsogenic response, i.v. hypertonic saline induced c-fos expression in the anterior third ventricle region, a putative dipsogenic center, as well as in the fetal hindbrain. The stimulation of fetal swallowing under conditions of higher osmotic stimulation and the correlation with forebrain c-fos expression indicates that near-term fetal osmoregulation mechanisms are functional, although not completely mature. Intravascular osmolality and body fluid homeostasis are maintained primarily by coordination of thirst-mediated drinking behavior and neuroendocrine-mediated renal fluid regulatory mechanisms. During in utero development, fetal swallowing contributes importantly to amniotic fluid volume homeostasis. Previous studies in this laboratory have demonstrated that near-term ovine fetal swallowing is stimulated by intravenous, intracarotid, and intracerebroventricular hyperosmolality (1-4), consistent with the activation of central osmoreceptors in regions responsive to both vascular and cerebrospinal fluid tonicity. Despite intact fetal osmotic-dipsogenic responsiveness, fetal swallowing is not stimulated in response to plasma osmolality increases (2 to 3%), which typically stimulate adult drinking behavior. For example, despite continually elevated plasma osmolality (10 -14 mosmol/kg) in response to short-term i.v. hypertonic saline injection, fetal swallowing activity is only stimulated for a maximum of 5 min (1). Furthermore, long-term increases in plasma osmolality of 10 mosmol/kg do not alter fetal swallowed volume (5). These responses suggest either a reduced population of fetal osmoreceptor cells, reduced sensitivity of osmoreceptors, or altered secondary neural mechanisms, in comparison to the adult. c-fos expression has been well described as a marker of neuronal activation in both adult and fetal brain nuclei (6). McDonald et al. (7) recently showed that FOS-ir was evident in the SFO, OVLT, and MnPO, as well as in the PVN and SON of the near-term fetal forebrain in response to maternal hypertonicity. These results are comparable to physiological and c-fos responses observe...