Stimulation of alpha(2)-adrenoceptors and kappa-opioid receptors increases the ultrasonic vocalizations of preweanling rats. The purpose of the present study was to determine whether alpha(2)-adrenoceptors and kappa-opioid receptors modulate ultrasonic vocalization production via a common mechanism. To that end, 11-day-old rats were injected with the alpha(2)-adrenoceptor antagonist yohimbine (0, 0.5, or 1.0 mg/kg, i.p.) or the kappa-opioid receptor antagonist nor-binaltorphimine (0, 5, or 10 mg/kg, i.p.). After 15 min, the same rats were injected with saline, the alpha(2)-adrenoceptor agonist clonidine (0.25 mg/kg, i.p.), or the kappa-opioid receptor agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methanesulfonate (U-50,488; 2.5 mg/kg, i.p.). Results showed that both clonidine and U-50,488 increased the ultrasonic vocalizations of preweanling rats. Not surprisingly, clonidine-induced ultrasonic vocalizations were blocked by yohimbine, while U-50,488-induced vocalizations were blocked by nor-binaltorphimine. Importantly, yohimbine also attenuated the vocalizations produced by U-50,488, whereas nor-binaltorphimine did not alter clonidine-induced ultrasonic vocalizations. Thus, it appears that alpha(2)-adrenoceptor and kappa-opioid receptor stimulation increases ultrasonic vocalization production via a common mechanism. It is likely that the kappa-opioid receptors responsible for modulating ultrasonic vocalizations are located "upstream" from the alpha(2)-adrenoceptors.