Two α1-adrenergic receptor (AR) subtypes have been defined by pharmacological studies in rat tissues, the α1A and the α1B, whereas three α1-ARs have been cloned, α1B, α1C, and α1D. It has been reported that α1C mRNA is absent in all rat tissues, making uncertain the correspondence of this cloned subtype, if any, to the native α1-ARs defined by pharmacological criteria. In the present study, a partial α1C-AR cDNA was obtained from rat cardiac myocytes using RT-PCR with degenerate primers. A sensitive RNase protection assay was used to map the distribution of α1C mRNA in adult rat tissues, in comparison with α1B and α1D. α1C mRNA was abundant in heart, brain, aorta, vena cava, vas deferens, submaxillary gland, lung, and kidney; was detected at lower levels in prostate, parotid gland, and skeletal muscle; and was undetectable in liver and spleen, α1B and α1D mRNAs were present in most of the same tissues. In contrast to α1C, however, α1B and α1D were both present in spleen; α1B was the sole al-AR mRNA in liver; and α1D mRNA was not detected in submaxillary gland, a tissue known to be enriched in the pharmacological α1A. We conclude that the distribution of α1C-AR mRNA in rat tissues is compatible with the idea that the α1C corresponds to the classical native α1A-AR. Although many tissues contain all three α1-AR mRNAs, distinct tissue-specific expression is evident. © 1994 Academic Press, Inc.