Octopamine-2 receptors, associated with activation of adenylate cyclase, mediate a number of the important hormonal and neurotransmitter functions of octopamine in invertebrates. By utilizing the highly enriched octopamine-sensitive adenylate cyclase present in the firefly light organ, it has been possible to pharmacologically characterize octopamine-2 receptors and to define a new class of highly potent and selective octopamine-2 agonists. At low concentrations, these substituted phenyliminoimidazolidines stimulate light emission when injected into fireflies. At somewhat higher concentrations, these compounds, when ingested by tobacco hornworms, cause disruption of motor and feeding behavior, leading to insect death. The effects of these compounds are markedly potentiated by phosphodiesterase inhibitors and mimicked by other activators of octopamine-sensitive adenylate cyclase, including octopamine itself. Because octopamine-2 receptors appear to be present primarily in invertebrates, these findings, together with other data, raise the possibility that potent and selective octopamine agonists could be useful as insect toxins with low toxicity in vertebrates.