The role of cyclic AMP and calcium in the mediation of the effects of octopamine has been investigated in the extensor tibiae muscle of the hind leg of the locust. Elevation of cyclic AMP levels in the preparation by means of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), by means of the diterpene adenylate cyclase activator, forskolin, and by means of cyclic nucleotide analogues mimics the post-synaptic effects of octopamine application at different frequencies of neuronal stimulation. These conditions also mimic the presynaptic effects of octopamine on spontaneous release of transmitter from the slow motoneurone. The effects of octopamine on the preparation are calcium sensitive, with the maximal sensitivity occurring between 0.5 and 4.0 mM-external calcium. The results are discussed in terms of the role of cyclic AMP and calcium in the mediation of the effects of octopamine.