Further studies are obviously necessary for a better understanding of the role of cyclic AMP- and cyclic GMP-dependent mechanisms in the central nervous system. The present, already voluminous literature provides many indications of important roles for cyclic AMP in (1) establishment of the synaptically integrated central nervous system, (2) inhibitory regulation of membrane properties and hence of neuronal activity and responsiveness, (3) control of synthesis and release of neurotransmitter substances and mediation of their effects, (4) regulation of metabolic function, (5) feedback control of its own formation and action through alterations in adenylate cyclase, phosphodiesterase, and kinase activity, and (6) interactions with calcium ions. Alterations of cyclic AMP-generating systems in response to changes in synaptic input would appear to be fundamental to one aspect of adaptation in the central nervous system. Roles for cyclic GMP in the stimulatory regulation of neuronal activity and responsiveness have been indicated. Little evidence for interrelationships between cyclic AMP and cyclic GMP mechanisms have been provided in brain tissue. Further insights into the precise nature and role of cyclic nucleotide mechanisms and correlations with physiological functions and with the relevant morphological entities in which cyclic AMP or cyclic GMP serve as regulatory messengers of such functions in the central nervous system remain a challenge for the future.