Serotoninergic axons in the cat cerebral cortex were demonstrated immunohistochemically with a monoclonal antibody to serotonin (5-HT). Three types of 5-HT axons are distinguished at the light microscopic level by differences in their morphology. Small varicose axons are fine (less than 0.5 micron) and bear fusiform varicosities that are generally less than 1 micron in diameter. These axons extend throughout the width of the cortex and branch frequently, giving rise to widely spreading collaterals. Nonvaricose axons are smooth, show a relatively large and constant caliber (about 1 micron), travel in straight, horizontal trajectories, and branch infrequently. Large varicose axons are distinguished by large round or oval varicosities (1 micron or more in diameter) borne on fine-caliber fibers. These axons often form basket-like arbors around the somata of single neurons. In the simplest basket-like arbors, several large, round varicosities from a small number of axons contact the soma. In complex baskets intertwining collaterals contact the soma and apparently climb along and outline the cell's major dendrites. The patterns revealed by the climbing axons suggest that a variety of nonpyramidal cell types selectively receive dense 5-HT innervation. Serial reconstructions of the 5-HT axons within the cortex show that the large varicose axons arise as infrequent collaterals from the nonvaricose axons. A single nonvaricose parent axon gives rise to several large varicose axon collaterals that may contribute to different basket-like arbors. Conversely, a single basket-like arbor may be formed by large varicose axon collaterals from more than one nonvaricose parent axon. The small varicose axons do not appear to be related within the cortex to either the nonvaricose or large varicose axon types. The results support the hypothesis that the 5-HT projection to the cortex is organized into two subsystems, one of which may exert widespread influence in the cortex via highly divergent branches, while the other, with a more restricted distribution, acts on specific classes of cortical neurons.