It has been demonstrated that adipocytes express high affinity ACTH and alpha-MSH binding sites, and that ACTH, alpha-MSH, and beta-LPH are potent lipolytic hormones. Considerable species variability exists in the lipolytic response to melanocortins, however. Recently, MC2 and MC5 receptor-mRNA was found in both murine adipocytes and in the 3T3-L1 murine embryonic fibroblast cell line, but only after the 3T3-L1 cells had differentiated into adipocytes. The 3T3-L1 cell line was used to characterize the pharmacological properties of both MC2 and MC5 receptors in situ. Both murine MC2 and MC5 receptors are functional in the adipocyte, although the MC5 receptor required high doses of alpha-MSH to activate cylase. ACTH potently stimulates cyclase with EC50 values that are consistent with the hypothesis that the murine MC2 receptor, not the MC5 receptor, mediates stress-induced lipolysis via release of ACTH from the pituitary.