Distress vocalizations were produced in adult guinea pigs by electrical stimulation of the dorsomedial thalamus or the septum-preoptic area. Both of these forebrain-derived vocalizations were increased by systemic administration of naloxone and were inhibited by analgesic periventricular gray stimulation. Naloxone blocked the inhibitory effects of the analgesic stimulation on thalamic vocalizations. Stimulation of nonanalgesic mesencephalic sites in close proximity to the periventricular gray increased the anterior-elicited vocalizations. These data provide evidence for ascending endorphin-mediated inhibition of excitatory forebrain sites for distress vocalizations.