Neuronal activity may lead to a variety of responses in neighbouring glial cells; in general, an ensemble of neurons needs to be active to evoke a K+- and/or neurotransmitter-induced glial membrane potential change. We have now detected a signal transfer from a single neuromodulatory Leydig neuron to the giant neuropil glial cells in the central nervous system of the leech Hirudo medicinalis. Activation of a Leydig neuron, two of which are located in each segmental ganglion, elicits a hyperpolarization in the giant neuropil glial cells. This hyperpolarization could be mimicked by bath application of the peptide myomodulin A (1 nM-1.0 microM). Myomodulin-like immunoreactivity has recently been found to be present in a set of leech neurons, including Leydig neurons (Keating & Sahley 1996, J. Neurobiol., 30, 374-384). The glial responses to Leydig neuron stimulation persisted in a high-divalent cation saline, when polysynaptic pathways are suppressed, indicating that the effects on the glial cell were direct. The glial responses to myomodulin A application persisted in high-Mg2+/low-Ca2+ saline, when chemical synaptic transmission is suppressed, indicating a direct effect of myomodulin A on the glial membrane. The glial hyperpolarization evoked by myomodulin A was dose dependent (EC50 = 50 nM) and accompanied by a membrane conductance increase of approximately 25%. Ion substitution experiments indicated that myomodulin A triggered a Ca2+-independent K+ conductance. Thus, our results suggest, for the first time, direct signal transmission from an identified modulatory neuron to an identified glial cell using a myomodulin-like peptide.