In this article 8 male Wistar rats received bilateral lesions of the medial prefrontal cortex, whereas another 8 rats were control operated. Three weeks after surgery, they were exposed to an autoshaping procedure in which the insertion of a lever into the experimental chamber (conditioned stimulus) always preceded the delivery of a response-independent food pellet (unconditioned stimulus). Subjects with lesions acquired this conditional association faster than control-operated subjects as evidenced by the fact that they were more likely than control-operated subjects to contact the conditioned stimulus at higher rates. Locomotor activity, observed in a standard open-field preceding autoshaping sessions, decreased for both groups of subjects with repeated exposure to the open-field, whereas differences between groups were not observed. The same subjects were also exposed to an operant delayed spatial response alternation procedure in which they were required to alternate responding between two levers that were inserted into the experimental chamber after delay intervals of either 5, 10, or 20 s had elapsed. Alternation response accuracy of both subjects with lesions and control subjects decreased as a function of the duration of the delay interval, but control-operated subjects responded more accurately than did lesion subjects at each interval duration. Response accuracy increased with prolonged training for both groups of subjects, but faster for control-operated than for subjects with lesions.(ABSTRACT TRUNCATED AT 250 WORDS)