Multiple subtypes of alpha adrenergic receptors with CNS expression (alpha 1A, alpha 1B, alpha 2A and alpha 2C) have been identified through pharmacological and molecular biological means. To characterize the localization of these subtypes and attempt to correlate subtype expression with physiological significance, the expression of the mRNAs encoding the alpha 1A, alpha 1B, alpha 2A and alpha 2C adrenergic receptor subtypes was examined in the adult rat brain by in situ hybridization histochemistry. Each subtype demonstrated a unique pattern of distribution, with the alpha 1 adrenergic receptors more restricted in their distribution and the alpha 2 receptors more widespread. The alpha 1A was primarily localized in the olfactory bulb, intermediate layers of the cortex, the hippocampus and the reticular nucleus of the thalamus. The alpha 1B was expressed in intermediate and deep layers of the cortex, thalamus, hippocampus, dorsal raphe and cerebellum. Although the alpha 2A message was relatively low in abundance, it was identified in the olfactory bulb, cortex, hippocampus, locus coeruleus, pons and cerebellum. The alpha 2C messenger RNA was localized in the cortex (particularly cingulate), hippocampus, caudoputamen, pons and cerebellum. Multiple alpha adrenergic receptor subtypes have significant sequence homology and similar pharmacologic properties; however, they each possess a unique pattern of messenger RNA distribution throughout the brain. The multiplicity of subtypes of alpha adrenergic receptors in specific brain regions may dictate the physiological and pharmacological responses to catecholamines.