Neural mechanisms in the temporal lobe are essential for recognition memory. Evidence from human functional imaging and neuropsychology, and monkey neurophysiology and neuropsychology also suggests a role for prefrontal cortex in recognition memory. To examine the interaction of these cortical regions in support of recognition memory we tested rhesus monkeys with prefrontal-inferotemporal (PFC-IT) cortical disconnection on two recognition memory tasks, a "constant negative" task, and delayed nonmatching-to-sample (DNMS). In the constant negative task monkeys were presented with sets of 100 discrimination problems. In each problem one unrewarded object was presented once every day, and became familiar over the course of several days testing. The other, rewarded object was always novel. In this task monkeys learned to avoid the familiar constant negatives and choose the novel objects, so performance on this task is guided by a sense of familiarity for the constant negatives. Following PFC-IT disconnection monkeys were severely impaired at reacquiring the rule (to avoid familiar items) but were subsequently unimpaired at acquiring new constant negative problems, thus displaying intact familiarity recognition. The same monkeys were impaired in the acquisition of the DNMS task, as well as memory for lists of objects. This dissociation between two tests of recognition memory is best explained in terms of our general hypothesis that PFC-IT interactions support the representation of temporally complex events, which is necessary in DNMS but not in constant negative. These findings, furthermore, indicate that stimulus familiarity can be represented in temporal cortex without input from prefrontal cortex.