Melanocortin peptides exert pleiotropic effect in numerous cell types, controlling processes ranging from adrenal steroidogenesis and melanocyte pigmentation to lacrimation and nerve regeneration. The binding of melanocortins to specific cell surface receptors initiates cellular responses via GTP binding proteins (G-proteins). The affinity of these peptides to the receptor is modulated by extracellular Ca2+ ions, a property unique to melanocortin receptors. In astrocyte cultures derived from the rat brain, melanocortin stimulation elevates cAMP levels that appear to induce morphological changes. However, a transient proliferative response to melanocortins in these cells appears to be cAMP independent. The presence of melanocortin receptors in brain tissue and their unique Ca2+ dependence are discussed in relation to their putative role as regulators of astrocytes.