To determine the influence of intrinsic medial prefrontal cortex (MPFC) neurons on regional brain catecholamine turnover, dopamine (DA) and its metabolites were assayed in several brain areas 14 and 28 days after bilateral ibotenic acid (IA) lesions of the MPFC in the rat. The locomotor response to D-amphetamine was also assessed. On the 14th postoperative day levels of DA, homovanillic acid concentrations and 3,4-dihydroxyphenylacetic acid were elevated in the anterior striatum of IA-lesioned animals. Spontaneous and amphetamine-induced locomotion were also increased. These changes disappeared by the 28th postoperative day. It is concluded that destruction of the efferents of the MPFC induces transient increases in DA turnover within the medial striatum and transiently increases spontaneous and amphetamine-induced locomotion.