The three major strategies for transmembrane signalling at the plasma membrane level involve either second messengers, ion channels or receptor-mediated endocytosis. Two second-messenger types of transmembrane signalling systems have been analyzed: the adenylate cyclase and protein kinase C systems. Both are triggered by a variety of biological signals and eventually activate a specific protein kinase. The pathogenic stimulation of adenylate cyclase and protein kinase C systems by cholera toxin and tumor promoters, respectively, is described.