Octopamine increases the level of cyclic AMP in a dose-dependent way in the locust extensor tibiae neuromuscular preparation. The response peaks after a 10 min exposure and then declines to a plateau. The effect of octopamine is potentiated in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). The levels of cyclic GMP in the muscle were not affected by octopamine. The response is stereospecific for the naturally occurring D(-) isomer of octopamine and is also specific for monophenolic biogenic amines. Studies with a range of synthetic agonists and antagonists reveal that the receptors mediating the response are of the OCTOPAMINE2 class. Forskolin, a diterpene activator of adenylate cyclase activity, increases cyclic AMP but not cyclic GMP levels in the extensor muscle. The response has a prolonged time course and is again potentiated by IBMX. Stimulation of the octopaminergic neurone to the extensor muscle increases the levels of cyclic AMP but not those of cyclic GMP. The response is blocked by phentolamine, an alpha-adrenergic blocking agent that also blocks the effects of octopamine in this preparation. The results are discussed in terms of the parallels between the biochemical and physiological effects of octopamine on this muscle and in terms of the mode of action of the octopamine receptors present.