The intergenic region (IGR) separating the genes for vasopressin (VP) and oxytocin (OT) has been shown to be critical for the cell-specific expression of these peptide genes in hypothalamic neurons. To date, the most relevant information about the putative cis-elements in the IGR that might determine cell-specific gene expression has come from studies in transgenic models. As a first step toward increasing the efficiency of the IGR sequence deletion studies in transgenic animals, a comparative genomics approach comparing the IGR sequence in humans versus mice was used to identify conserved sequences that might be candidate regulatory elements. The nucleotide sequence of the IGR between the human VP and OT genes was determined and compared to the mouse IGR, and 26 conserved sequences in three distinct clusters were found. These conserved sequences and motifs may be important for the cell-specific expression of the VP and OT genes. However, before further significant progress can be made, a "high-throughput" method for the analysis of deletion constructs in relevant cell types in vitro is needed. It is proposed here that organotypic culture models combined with the use of particle-mediated gene transfer methods may provide an effective, general strategy for the study of cell-specific expression in the central nervous system.