We have shown previously that ibotenic acid lesions of the prefrontal cortex, performed prior to repeated amphetamine administration, do not affect sensitization of stereotyped behaviors but do prevent sensitization of post-stereotypy locomotor hyperactivity [Wolf et al., Neuroscience, 69 (1995) 417-439]. This could reflect an effect of the lesion on either development orexpression of locomotor sensitization. To test the latter possibility, rats were treated with repeated amphetamine injections and tested to establish behavioral sensitization. Then, half received ibotenic acid lesions of prefrontal cortex and half received sham lesions. A second amphetamine challenge, 7 days later, demonstrated that the lesion failed to prevent expression of sensitization. Together with previous results, this suggests that intrinsic neurons of prefrontal cortex, most likely those sending excitatory amino acid-containing projections to the ventral tegmental area, are required for the development but not the expression of behavioral sensitization to amphetamine.