This study was performed to investigate the physicological properties of histaminergic neurons in intraocular hypothalamic transplants. Pieces of posterolateral hypothalamus containing the tuberomammillary nucleus were dissected from Embryonic Day 17 rat fetuses and transplanted into the anterior chamber of the eye of adult rat hosts. The hypothalamic transplants were left to mature for 2-5 months, after which in vivo electrophysiological recordings were performed. Extracellular recordings revealed spontaneously active neurons in the grafts, with a mean (+/- SEM) firing rate of 2.8 +/- 2.0 Hz and a mean action potential duration of 1.2 +/- 0.5 ms. When the surface of the grafts was superfused with histamine, the neuronal activity was depressed at concentrations above 30 microM. Superfusion with the H3 agonist (R)-alpha-methylhistamine also elicited depression of baseline firing rate, with an EC50 of 0.435 microM. This depression could be antagonized by superfusion with the H3-receptor antagonist thioperamide. In studies of histamine levels using a sensitive radioenzymatic assay, the mean (+/- SEM) level of histamine in the grafts was 73 +/- 28 ng/g tissue, i.e., about half the concentration of histamine in the adult rat hypothalamus in situ. Intracellular recordings in combination with biocytin labeling and histidine decarboxylase immunohistochemistry suggested that the grafted neurons from which recordings were made were histaminergic. Taken together, these data indicate that tuberomammillary neurons continue their development in intraocular transplants and develop physiological characteristics found in these neurons in situ.