The CL is an organ that exhibits extremely rapid growth, development and regression during the course of each nonpregnant cycle. The CL consists of small and large steroidogenic cells as well as nonsteroidogenic cells including endothelial cells, pericytes, fibroblasts and immune cells. Cellular interactions among these cell types may be coordinated by several mechanisms, including contact-independent (humoral) and contact-dependent (gap junctional) pathways. Gap junctions and the proteins (connexins) composing them are present in luteal tissues of several species. Expression of connexins and the rate of gap junctional intercellular communication (GJIC) are affected by the stage of luteal development and regulators of CL function. Connexin (Cx)26 and Cx32 are present in the cytoplasm and on the borders of cells within parenchymal lobules and connective tissue tracts of the CL; Cx43 is located mostly in the parenchymal areas on the cellular borders between steroidogenic and nonsteroidogenic cells. Expression of Cx43 protein is greatest in early and mid-cycle CL. In vitro, LH and cAMP stimulates GJIC of luteal cells. Prostaglandin F2 (PGF) does not affect basal GJIC but decreases stimulatory effects of LH on GJIC. A cAMP antagonist decreases GJIC of luteal cells, protein kinase C activator and a calcium ionophore inhibit GJIC of luteal cells. In vivo administration of LH increases but PGF decreases basal GJIC of small-to-small and large-to-small luteal cells and progesterone (P4) secretion by luteal cells from mid-luteal phase of the estrous cycle. Moreover, transfection of bovine luteal cells with Cx43 antisense oligonucleotide decreases LH-induced GJIC and P4 secretion. These data indicate that gap junctions are involved in regulating P4 production in the CL. Thus, gap junction mediated-cellular interactions are likely important in coordinating a variety of luteal functions including hormone production, signal transduction, tissue growth, regression and angiogenesis. Supported by NIH grant 1R29 HD30348, NSF grants MCB-9306241 and ERH9108770, and USDA grants 93-37208-9224, 93-37203-9271, 96-35203-3269 and 98-02168.