We have proposed that short (<0.5 s), high-frequency (approximately 50 kHz) ultrasonic vocalizations ("50-kHz USVs") index a positive affective state in adult rats, because they occur prior to rewarding social interactions (i.e., rough-and-tumble play, sex). To evaluate this hypothesis in the case of nonsocial stimuli, we examined whether rats would make increased 50-kHz USVs in places associated with the administration of rewarding pharmacological compounds [i.e., amphetamine (AMPH) and morphine (MORPH)]. In Experiment 1, rats made a greater percentage of 50-kHz USVs on the AMPH-paired side of a two-compartment chamber than on the vehicle-paired side, even after statistical correction for place preference. In Experiment 2, rats made a higher percentage of 50-kHz USVs on the MORPH-paired side than on the vehicle-paired side, despite nonsignificant place preference. These findings support the hypothesis that 50-kHz USVs mark a positive affective state in rats and introduce a novel and rapid marker of pharmacological reward.