The influenced of ACHT4-10, a behaviourally active fragment of adrenocorticotropic hormone (ACTH) devoid of endocrine activity, on synaptic transmission in the paravertebral sympathetic ganglion of the frog was investigated. Postsynaptic potentials evoked by electrical stimulation of preganglionic nerves were recorded using a surcrose gap method. Fast excitatory postsynaptic potentials (EPSPs), which are mediated via nicotinic cholinergic synapses, were not affected by 10-6 M ACTH4-10. Application of ACTH4-10 in a concentration as low as 10-8 M for 60 min caused a marked augmentation of the amplitude of slow inhibitory postsynaptic potentials (IPSP) which are mediated via dopaminergic synapses. The increase in amplitude developed gradually after a latency of 60-90 min and outlasted the application of the peptide. In addition, ACTH4-10 at 10-6 M increased the hyperpolarising response of the gangalion to exogenous dopamine, as studied by a micro-application method. There was no significant effect of ACTH4-10 on the muscarinic cholinergic depolarising response of the ganglion towards exogenous acetylcholine. The behaviourally active vasopressin fragment DG-LVP (10-6 M) had no effect on slow IPSPs. The results demonstrate that ACTH4-10 specifically affects slow synpatic inhibition in frog sympathetic ganglion, probably by acting upon the postsynaptic membrane. The possibility is discussed that ACTH-10 affects one of the intermediate steps between dopaminergic receptor interaction and generation of the slow IPSP. © 1979.