The c- fos protein is rapidly induced in hypothalamic magnocellular nuclei following hemorrhage. We used specific antibodies directed against c- fos and either vasopressin (AVP) or oxytocin (OT) neurophysin to investigate c- fos activation in individual AVP and OT neurons. AVP and OT neurons expressed c- fos in response to hypovolemic stimuli. Following a protocol of incremental hemorrhage, AVP and OT neurons expressed c- fos with a graded response that correlated with stimulus intensity. As the volume of hemorrhage increased, there was an increase in the number of cells expressing c- fos as well as in the amount of c- fos immunoreactivity per cell. These increases correlated with the amount of hormone released into the peripheral blood. In addition, a differential pattern of activation for AVP neurons occurred in response to hemorrhagic stimuli. AVP neurons in the supraoptic nucleus (SON) had a lower threshold for response than those in the paraventricular nucleus (PVN). For OT, activation required a greater blood loss than AVP and c- fos expression encompassed both SON and PVN neurons. We conclude that c- fos expression is proportional to stimulus intensity and reveals functional heterogeneity among magnocellular neurons.