Several cDNA clones encoding the human neuropeptide Y-Y1 receptor have been isolated that contain differing sequences at their 5'-ends. The divergence occurs at a splice junction in the 5'-untranslated region, suggesting that at least three forms of the neuropeptide Y-Y1 receptor transcript are generated by alternative splicing at this site. Genomic clones have been isolated that encompass the alternatively spliced 5'-exons. The exons are found 6.4, 18.4, and 23.9 kilobases upstream of exon 2. In the corresponding promoter regions of the various exons, possible response elements for the glucocorticoid receptor, as well as potential binding sites for the AP-1, AP-2, and NF-kappa B transcription factors are found. Analysis of NPY-Y1 transcripts in various cell types demonstrates the tissue-specific activation of the three promoters.