Histamine neurons acutely dissociated from the tuberomammillary nucleus of the rat hypothalamus were studied in whole-cell and cell-attached patch-clamp experiments. Electrophysiological properties of dissociated cells were found to be similar to those recorded in slice experiments using microelectrodes. Tuberomammillary neurons fired spontaneously and this activity persisted when Cs+ (1.5 mM) was added to, or when K+ was removed from the extracellular solution. In whole-cell experiments a persistent tetrodotoxin-sensitive inward current was recorded. In cell attached recordings voltage-gated sodium channels displayed either normal or non-inactivating behavior. These results provide a further analysis of the properties of histaminergic neurons and indicate that spontaneous activity is intrinsic to individual neurons. Evidence for a non-inactivating tetrodotoxin-sensitive sodium current is presented. Single channel recordings indicate that this current is the result of non-inactivating behavior of sodium channels. Such a current is well suited for biasing tuberomammillary neurons toward spontaneous activity.