One open reading frame of a 13 kb genomic clone of the human beta 1-adrenergic receptor, which lacks introns, encodes the previously isolated cDNA. Transcript(s) between 4.7 and 5.1 kb are detected in total RNA, whereas a approximately 3 kb transcript is detected only in polyadenylated RNA. The poly (A+) transcript is most highly expressed in the pancreas, liver, heart, kidney, thalamus, adrenal, and salivary glands. Primer extension and ribonuclease protection analyses suggest that the major transcriptional start site is located at -263. Transient expression of luciferase reporter gene constructs indicates that the region from -444 to -360 possesses the primary promoter, consistent with the transcriptional start site at -263. Negative transcriptional regulatory elements are located from -3118 to -2730 and -2730 to -2241, while a positive element is located between -2241 and -1790. The present study suggests that, despite similarities, the expression and transcriptional regulation of the human gene are distinct from those of the genes of other species.