Intrinsic neuron-like cells expressing the catecholamine-biosynthetic enzyme tyrosine hydroxylase (TH) have recently been identified in the testis of the prepubertal rhesus monkey. The aims of this study were to characterize the neuron-like nature of these cells, and to examine the distribution and frequency of testicular neuronal elements during postnatal development, puberty, adulthood and old age. Using immunohistochemistry, nerve fibers and cell bodies immunoreactive for the neuronal markers neurofilament 200 (NF-200) and synaptosomal associated protein of 25 kDa (SNAP 25), TH and neuropeptide Y, were identified in perivascular locations, intermingled with interstitial Leydig cells and close to the wall of seminiferous tubules. Moreover, marked age-related differences in the numbers of these neuronal elements became apparent when the NF-200 immunoreactive neuronal elements were quantified. Thus, intrinsic neuron-like cell bodies were found only in the testes fro m immatu re animals (<3 years of age). Conversely, nerve fibers were observed at all ages, although they became more prominent after the pubertal increase in LH and testosterone levels. Interestingly, mast cells, which are known to contain potent regulatory substances, were found in close anatomical proximity to nerve fibers. The number of these cells, positively identified with an antibody to tryptase, increased significantly after puberty following the same developmental pattern as the nerve fibers. These results confirm that the testicular nervous system of the monkey comprises two components, intrinsic nerve cells and extrinsic fibers, both of which are catecholaminergic and peptidergic in nature. Furthermore, both components are highly plastic during development, suggesting a possible participation in the onset of puberty. The intratesticular locations of neuron-like cells and fibers suggest that catecholamines and neuropeptides may have multiple sites of actions, and may affect Leydig cel ls, cells of the tubular wall, and vascular cells directly and/or indirectly via intermediation of mast cells. FUNDING Nonfederal Institutional funds PUBLICATIONS Lue YH, Sinhahikim AP, Machida Y, Mayerhofer A, Urbanski HF, Wang C, Swedloff RS. Accelerated germ cell apoptosis in aging rhesus monkeys. In Endocrine Society Program & Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 381, 1998 (abstract). Frunigieri M, Urbanski HF, Calandra R, Mayerhofer A. Elmentos neuronales testiculares en el mono. Medicina Buenos Aires 58:438, 1998 (abstract).