Prairie voles (Microtus ochrogaster) are a socially monogamous rodent species and their cooperative behaviors require extensive communication between conspecifics. Rodents use ultrasonic vocalizations (USVs) to communicate and because a prairie vole breeder pair must engage in extensive cooperation for successful reproduction, auditory communication may be critical for this species. Therefore, we sought to characterize USVs in adult male and female prairie voles, and to determine how these calls are influenced by social context, salient social stimuli and the psychostimulant drug of abuse amphetamine (AMPH). Here, we characterize prairie vole USVs by showing the range of frequencies of prairie vole USVs, the proportion of various call types, how these call types compare between males and females, and how they are influenced by social stimulation and AMPH. AMPH caused a robust increase in the number of USVs in both males and females and there was a dramatic sex difference in the complexity of call structures of AMPH-induced USVs, with males emitting more elaborate calls. Moreover, we show that novel (i.e. salient) social cues evoked differential increases in USVs across sex, with males showing a much more robust increase in USV production, both with respect to the frequency and complexity of USV production. Exposure to an estrous female in particular caused an extraordinary increase in USVs in male subjects. These data suggest that USVs may be a useful measure of social motivation in this species, including how social behaviors can be impacted by drugs of abuse.