In these studies the incidence of conditioned and unconditioned 50-kHz ultrasonic vocalizations (USVs) in young rats was measured in response to rewarding manual tickling by an experimenter. We found that isolate-housed animals vocalize much more then socially housed ones, and when their housing conditions are reversed, they gradually shift their vocalization tendencies. Isolate-housed animals also show quicker acquisition of instrumental tasks for tickling, and exhibit less avoidance of tickling as compared to socially housed Ss. Isolate-housed animals also show rapid acquisition of 50-kHz USVs to a conditioned stimulus that predicts tickle reward, while socially housed animals do not. We successfully bred for high and low vocalization rates in response to tickling within four generations. The high tickle line showed quicker acquisition of an instrumental task for, as well as less avoidance of, tickling as compared to the random and low tickle lines. They also played more. Lastly, we found that the glutamate antagonist MK-801 can reduce tickle-induced 50-kHz USVs, but is resistant to opioid, dopamine and cholinergic stimulant and blocking agents. Overall, these results suggest that tickle evoked 50-kHz USVs may be a useful behavioral marker of positive social affect in rats. Difficulties with such concepts are also discussed.