Results from previous studies have suggested that the hypothalamus modulates cardiorespiratory responses to hypoxia and/or hypercapnia. Many neurons in the caudal hypothalamus are stimulated by hypercapnia and hypoxia in vivo; however, it is not known if these responses are dependent upon input from other areas. Whole-cell patch and extracellular recordings from a brain slice preparation were used in the present study to determine the direct effects of hypoxia (5% CO2/95% N2 or 10% O2/5% CO2/85% N2) and hypercapnia (7% CO2/93% O2) on caudal hypothalamic neurons in vitro. Coronal sections (400-500 microns) were obtained from young Sprague-Dawley rats and placed in a recording chamber that was perfused with nutrient media equilibrated with 95% O2/5% CO2. Extracellular recordings demonstrated that hypoxia stimulated over 80% of the neurons tested; the magnitude of the response was dependent upon the degree of hypoxia. In addition, over 80% of cells that were excited by hypoxia retained this response during synaptic blockade. Hypercapnia increased the discharge frequency of 22% of the caudal hypothalamic neurons that were studied. A second set of caudal hypothalamic neurons were studied with whole-cell patch recordings; the mean resting membrane potential of these neurons was -51.8 +/- 1.0 mV with an average input resistance of 399 +/- 49 M omega. Hypoxia produced a depolarization in 76% of these neurons; a poststimulus hyperpolarization often occurred. A depolarization and/or increase in discharge rate during hypercapnia was observed in 35% of the neurons tested. Only 10% of all neurons studied were excited by both hypoxia and hypercapnia. These findings suggest that separate subpopulations of caudal hypothalamic neurons are sensitive to hypoxia and hypercapnia. Thus, this hypothalamic area may be a site of central hypoxic and hypercapnic chemoreception.