Using intracellular recordings in guinea pig brain slices, the pharmacology of electrophysiologically identified and immunohistochemically confirmed non-cholinergic nucleus basalis neurons was studied to determine their response to the major neurotransmitters of the subcortical afferents to this region. The cells were differentiated into three types: Type A cells (approximately 44%) were depolarized by noradrenaline (NA) and muscarine, Type B cells (approximately 23%) were depolarized by NA but hyperpolarized by muscarine, and Type C cells (approximately 15%) were hyperpolarized by both agonists. These cell types were also differentially responsive to serotonin (hyperpolarizing B, C) and histamine (depolarizing A, B). Accordingly, the non-cholinergic neurons share certain discharge properties but appear nonetheless to comprise distinct types which respond differentially to the major modulatory neurotransmitters and thus play potentially different roles in cortical modulation across the sleep-wake cycle.