Caveolins (Cav-1, -2, and -3) are a gene family of cytoplasmic membrane-anchored scaffolding proteins that: (i) help to sculpt caveolae membranes from the plasma membrane proper; and (ii) participate in the sequestration of inactive signaling molecules. In the adult, caveolin-1 and -2 are co-expressed and are most abundant in type I pneumocytes, endothelia, fibroblastic cells and adipocytes, while the expression of caveolin-3 is restricted to striated muscle cells. However, little is known regarding the genomic organization and developmental expression of the caveolin gene family. Here, using the mouse as a model system, we examine the chromosomal localization, the detailed intron-exon organization, and developmental expression pattern of the caveolin gene family. cDNAs encoding caveolin-1, -2, and -3 were used as probes to isolate murine genomic clones containing these genes. Fluorescence in situ hybridization (FISH) analysis using these genomic clones as probes reveals that all three caveolin genes are localized to murine chromosome 6. Specifically, caveolin-1 and -2 co-localize to chromosomal region 6-A2, while caveolin-3 is located within the chromosomal region 6-E1. Searches of the NCBI Human/Mouse Homology map indicate that murine region 6-A2 corresponds to human chromosome 7q31. As this region (6-A2/7q31) is the site of an as yet unidentified tumor suppressor gene(s), our mapping studies clearly define caveolin-1 and caveolin-2 as candidate genes that may be deleted at these loci. All three caveolin genes show similar intron-exon organization, with the last exon of each gene encoding the bulk of the known caveolin functional domains. The boundary position of the last exon is essentially identical in all three caveolin genes, suggesting that they may have arisen through gene duplication events. Developmentally, all three caveolins were expressed late during mouse embryogenesis as assessed by Northern and Western blot analysis. We examined the localization of the caveolin proteins in sections of day 16 mouse embryos using a well-characterized panel of antibody probes. Caveolin-1 and -2 were most abundantly expressed in the developing lung parenchyma, while caveolin-3 was most abundantly expressed in developing tissues that consist primarily of skeletal muscle cells. As the expression of all three caveolins in the adult is highest in terminally differentiated cell types, this is consistent with the idea that caveolins may be viewed as late markers of differentiation during embryogenesis.