α1-Adrenergic receptors (α1ARs) are virtually ubiquitous in human tissues and mediate important physiological functions as diverse as smooth muscle contraction, glycogenolysis, and myocardial inotropy. At least three α1AR subtypes (α(1A/D), α(1B), and α(1C)) have been described using molecular and pharmacological techniques. The identification of species heterogeneity (rat versus rabbit) in α1AR subtype distribution has made it imperative to determine the distribution of α1AR subtypes in human tissues. Accordingly, RNA extracted from human tissues was analyzed using RNase protection assays to determine α1AR subtype expression. Of the cloned α1ARs, α(1C)AR mRNA predominates in many human tissues (heart, liver, cerebellum, and cerebral cortex), in contrast to its restricted distribution in both rats and rabbits. α(1B)AR mRNA is present in highest concentrations in human spleen, kidney, and fetal brain. α(1A/D)AR mRNA is present in highest concentrations in human aorta and cerebral cortex. Hence, α1AR subtype mRNA distribution is tissue selective and differs from that reported for rats and rabbits. These results have potentially significant implications for understanding human adrenergic physiology and are important for the rational development of α1AR subtype-selective drugs.