Cholecystokinin immunoreactivity (CI) was demonstrated in the inner one third of the molecular layer of area dentata in the rat and 3 strains of mice. This part of the molecular layer coincides with the terminal field of the commissural-associational system (C/A-system). In rats there is also CI in the middle third of this layer where the medial perforant path terminates, but there is no CI in this area in any of the 3 strains of mice. Different selective lesions except those involving the hilus, did not change this staining pattern. Electrolytic lesions of the hilus removed the CI in the terminal field of the C/A-system. Similarly, after kainic acid injections, the CI in the C/A-zone is reduced to a degree that is proportional to the amount of damage of the hilus. In the rat these lesions produced virtually no change in the CI of the medial perforant path terminal zone. The predominant type of cell within the hilus is the mossy cell and the cells of this type contain CI. The mossy cells have both commissural and ipsilateral projections that terminate in the inner one third of the molecular layer. Other cell types within the hilus contain CI, such as basket cells, oviform-like and fusiform-like cells. However, there was no evidence that any of these cells had commissural projections. Apart from the mossy cells there are other cells with commissural projections such as those in regio inferior. However, there was no evidence that any of them contained CI or also gave rise to an associational projection to the inner one third of the molecular layer. Moreover, there was a difference in the distribution of commissurally projecting cells that contained CI in the rat as compared to the mouse brain. This difference is the same as that occurring in the distribution of mossy cells where in the rat cells are found throughout the hilus, with most close to, but never inside the granule cell layer as compared to the mouse where virtually all are at a central part of the hilus. Thus these results are consistent with the hypothesis that all mossy cells contain CI and are the sole source of the C/A-system. After X-ray irradiation of the neonatal rat it is known that only part of the infrapyramidal blade of the granule cell layer is formed.(ABSTRACT TRUNCATED AT 400 WORDS)