Examination of cholecystokinin-immunoreactive cells in the rat frontal cortex revealed the presence in layers I-VI of a non-uniform population ranging in size from small to large. All were also immunoreactive for GABA. The most commonly observed dendritic form of the small cells were bipolar or bitufted although some were multipolar and demonstrated vasoactive intestinal polypeptide and in a few case calretinin immunoreactivity. The large cells were multipolar or bitufted and lacked expression of vasoactive intestinal polypeptide and calretinin immunoreactivity but occasionally showed calbindin D28k immunoreactivity. Therefore, the cholecystokinin-immunoreactive cells could be divided into two distinct subpopulations depending on their chemistry and morphology. Our previous studies showed that GABAergic cells in the neocortex could be classified into at least three chemically different subgroups: (1) parvalbumin-containing cells; (2) somatostatin-containing cells (most of them also contain calbindin D28k); and (3) vasoactive intestinal polypeptide- and/or calretinin-containing cells. The present results indicated that the small cholecystokinin-immunoreactive non-pyramidal cells constitute a subset of the vasoactive intestinal polypeptide- and/or calretinin-containing cortical GABAergic cells. The large cells remain to be categorized.