A series of opiate compounds was tested for their ability to depress the probability that the protozoan Stentor coeruleus would contract in response to mechanical stimulation. Of these 13-endorphin proved to be the most effective. The depressive effect of ~-endorphin is concentration-dependent with an approximate E.C. 50 of 3.0 gM and time-dependent with the maximum depression occurring 15 min after drug exposure. The effect of 13-endorphin is blocked by the opiate antagonist naloxone and pertussis toxin suggesting that it is mediated by a G-protein coupled opiate receptor. 13-endorphin does not alter responding to photic or electrical stimuli indicating its action is specific to the mechanical stimulus transduction mechanism. In agreement with this conclusion, electrophysiological studies reveal that 13-endorphin decreases the amplitude of the mechanoreceptor potential without altering other membrane properties. Voltage clamp analysis shows that 13-endorphin acts by decreasing inward currents through the mechanoreceptor channel at transmembrane potentials between -70 and +20 mV without affecting the outward currents observed at more depolarized voltages. The fact that a mammalian neuromodulatory peptide is capable of producing a specific modulation of an ion channel in a unicellular eukaryote indicates that mechanisms of signal transduction and neuromodulation originated at an early stage in evolution.