Recent observations from in vitro rodent preparations suggest an important role for the serotonin-2A (5-HT(2A)) receptor in eupneic (basal) and gasping respiratory activities, although the precise role appears to be different in different preparations. Since these in vitro preparations are typically supplied with elevated (and different) levels of K(+) to increase neuronal excitability, the role of endogenous activation of 5-HT(2A) receptors in these respiratory behaviors under "normal" levels of extracellular K(+) ([K(+)](o)) requires clarification. The current study sought to evaluate the influence of [K(+)](o) on the 5-HT(2A) receptor-mediated effects on basal respiratory activity and the phases of the hypoxic ventilatory response (HVR), including ischemia-induced gasping in an arterially-perfused adult rat preparation. Our data demonstrate that at each level of [K(+)](o) examined, blockade of 5-HT(2A) receptors increases basal phrenic burst frequency, decreases basal phrenic burst amplitude, alters basal phrenic burst pattern, and eliminates the phases of the HVR. These data support an important role for 5-HT(2A) receptors in respiratory control, and indicate the their role is not dependent on the level of [K(+)](o).