GnRH interacts with a plasma membrane receptor to provoke gonadotropin release, as well as regulate numbers of its own receptor and target cell responsiveness. Receptor numbers are altered in different physiological states of the animal. Microaggregation of the GnRH receptor mimics all known actions of the releasing hormone, and therefore is viewed as an early step in the molecular mechanism of hormone action. Internalized hormone is neither necessary nor sufficient for stimulation of known releasing hormone actions. Evidence summarized in the present work suggests that Ca2+ serves a role as a second messenger for GnRH-stimulated gonadotropin release, and that it may be involved in receptor up-regulation in response to the releasing hormone. In the former role, diacylglycerols by their action on protein kinase C, in a fashion independent of the Ca2+ -calmodulin system, may act as a signal amplifier.