To determine if oxytocin (OT) may have a modulatory role on corticotropin-releasing factor (CRF) and vasopressin (AVP) mediated ACTH-cortisol release in women, serial experiments were performed in which saline, OT, AVP and CRF were administered singly or in combinations. OT administration (2 IU intravenous bolus followed by 111 mlU/min infusion for 3 h) maintained a circulating concentration of 7.7 × 10"8 Mand did not significantly influence basal, AVP or CRF-induced ACTH-cortisol release. In contrast, OT inhibited significantly the potentiating effect of AVP on CRF-stimulated ACTH-cortisol release. These findings suggest that OT and AVP may modulate, in a reciprocal fashion, the CRF-mediated ACTH release and support the contention that OT may be involved in the neuroendocrine response to stress in women.