The anterograde tracer Phaseolus vulgaris-leucoagglutinin was used to examine the organization of the projections to the striatum from medial prefrontal and frontal cortical areas in the rat with reference to their relation to cholecystokinin-like immunoreactivity in the striatum. Medial prefrontal cortical areas projected bilaterally, with an ipsilateral predominance, to the striatum. Most of the positive fibres were found in medial and ventral areas of the caudate-putamen and in the nucleus accumbens. Labelled fibres formed distinct patch-like arrangements throughout the dorsomedial striatum, whereas more ventrally the fibres were densely packed and spread to lateral areas. Almost no fibres were found in the dorsolateral aspects of the caudate-putamen. Cholecystokinin-like immunoreactivity in the striatum was diffusely distributed in the medial aspects, in fine punctate elements as well as in patches of fibres. Overlapping of corticostriatal clusters of fibres, from medial prefrontal cortex, with cholecystokinin-immunoreactive patches was found at all rostrocaudal levels studied, but predominantly in rostral areas. The overlap was present both in the ipsilateral and the contralateral side. Often the cluster of corticostriatal fibres was completely and precisely overlaid by a cholecystokinin-immunoreactive patch. At more caudal planes the overlap was only partial and in some instances cholecystokinin-positive patches "avoided" zones of dense corticostriatal fibre terminations. Frontal cortex injections of tracer gave rise to a network of fibres in the lateral aspects of the striatum, sparing the medial areas. No overlap with cholecystokinin-immunoreactive patches was found in these cases. These results suggest that a large number of cholecystokinin-containing striatal fibres originate in medial prefrontal cortical areas.