An antiserum directed against the human form of corticotropin-releasing factor (CRF) was utilized for immunohistochemical visualization of the distribution of this peptide in the inferior olivary nucleus and cerebellum of 2 monkey species (Saimiri sciureus, Macaca fascicularis). Colchicine pretreatment was not used. In both species, immunoreactivity was evident in the vast majority of neurons in the inferior olivary nucleus, with perikarya in the medial accessory olive exhibiting especially intense staining. In cerebellum, no labeled perikarya were present, but immunoreactive axons exhibiting the morphological characteristics of climbing fibers and their collaterals were observed in cortical and nuclear structures. In the cortex, most labeled axons were confined to the molecular and Purkinje cell layers. In the sagittal plane, individual axonal arbors originated from thick, isolated axons at the base of the molecular layer and repeatedly ramified as they extended toward the cortical surface. In coronal sections, only thin, paired profiles were present. Labeled processes also formed efflorescences in the granular layer of cortex and were evident as highly arborized axons in cerebellar nuclei. In each of these instances, the labeled elements resembled climbing fibers or their collaterals as visualized by other methods. Other labeled processes in the granular layer exhibited the morphological characteristics of mossy fiber axons. Immunoreactive, climbing-fiber-like axons were present in the molecular layer throughout the major regions of cerebellar cortex. However, the most intensely labeled of these axons were strikingly clustered within particular regions and parasagittal domains. In the vermis and intermediate zone, intensely labeled axons were present only within parasagittal zones similar in location to those defined by climbing fiber innervation from the medial accessory olive. Intensely labeled axons were also densely but uniformly distributed within the uvula, the medial region of the dorsal paraflocculus, and the dorsal region of the pyramis, areas that receive their climbing fiber input primarily from the medial accessory olive. Labeled fibers were much less dense and were not clustered in the lateral hemispheres. The present observation of CRF-like immunoreactivity in the monkey olivocerebellar pathway is compatible with the previous observation of CRF mRNA within olivary neurons of rat, baboon, and human (Young et al., 1986) and with recent immunohistochemical findings in rat (Sakanaka et al., 1987; Palkovits et al., 1987), cat (Cummings et al., 1988; Kitahama et al., 1988), sheep (Cummings et al., 1988), and human (Powers et al., 1987).(ABSTRACT TRUNCATED AT 400 WORDS)