Clones for six mammalian adenylyl cyclases have recently been isolated. One of these enzymes, the type I calmodulin-sensitive adenylyl cyclase, is neurospecific and is implicated in neuroplasticity. We propose that the type I adenylyl cyclase may be important for learning and memory because it allows Ca(2+)-amplified cAMP signals, synergism between Ca2+ and cAMP-activated kinases, and positive feedback regulation of Ca2+ channels by cAMP-dependent protein kinase.