Abstract Previous studies have implicated the tegmental pedunculopontine (TPP) nucleus in mediating the rewarding effects of opiates, food, and amphetamine, provided that animals are not in aversive motivational states induced by food — or drug — withdrawal. We wondered if bilateral TPP lesions could block the reinforcing effects of systemic cocaine in a place conditioning paradigm. Both lesioned and sham animals acquired cocaine place preferences. TPP-lesioned animals subsequently failed to acquire place preferences when conditioned with morphine, replicating previous data with TPP lesions. It is possible that our cocaine place conditioning protocol induced aversions during drug withdrawal, thus explaining the inability of TPP lesions to block conditioning. We looked for place aversions by conditioning animals at various times postinjection of cocaine. At no time point following drug withdrawal from cocaine were significant conditioned aversions observed. Cocaine's systemic motivational effects are mediated by a substrate separate from the TPP substrate underlying the rewarding effects of opiates, food, and amphetamine.