Electron-microscopic immunocytochemistry of serial thin sections showed that, in normal rats, approximately 50% of corticotropin-releasing factor (CRF) axons in the external zone of the median eminence contained vasopressin (AVP) and AVP precursor-derived peptides coexistent in the same secretory vesicles as CRF. The other 50% of the CRF axons contained little or no detectable AVP or AVP precursor-derived peptides. Differential activation of these subpopulations of CRF axons could provide a mechanism by which levels of CRF and AVP in portal plasma could be varied independently.