The timing, hemispheric laterality, and mode of termination of input from the prefrontal association cortex to the neostriatum were studied in fetal and neonatal rhesus monkeys using autoradiography for tracing connections. In addition, the cytological maturation of the neostriatum was examined in Nissl-stained sections from the same and other monkeys of selected prenatal and postnatal ages. A small contingent of corticostriatal axons reaches both the caudate nucleus and the putamen by the 69th embryonic day (E69) of the 165-day gestation period in this species and steadily expands over the next 3 fetal months. Throughout this period, ipsilateral perfrontostriatal connections predominate, and only a small and variable amount of label is detectable over the contralateral neostriatum. A major feature of the developing corticostriatal projection is a transfiguration in the distribution of its terminals: from E69 to E95, cortical terminals are distributed uniformly among neostriatal neurons; beginning around E105, areas of higher and lower grain density begin to emerge until finally, by E133, 250- to 500-micrometers-wide circular and elliptically shaped label- free cores perforate a field of densely labeled cortical terminals as in the neostriatum of the adult monkey (Goldman, P. S., and W. J. H. Nauta (1977) J. Comp. Neurol. 171: 369–386). The cytoarchitectonic composition of the neostriatum also changes during gestation: from E69 through E95, the small postmitotic neurons of the immature neostriatum are packed densely and, for the most part, are distributed homogeneously; by E105, they become segregated into cellular islands consisting of densely packed neurons that are encapsulated by fiber- rich annuli and embedded in a matrix of less densely arrayed neurons. The shape and size of the islands in Nissl-stained sections correspond to label-free cores in autoradiograms of fetuses with cortical injections, while the surrounding annuli and adjacent matrix cells correspond to areas of dense accumulation of label. Thus, the formation of the corticostriatal projection in primates involves a transformation in the distribution of ingrowing terminals synchronized with changes in cellular organization of the neostriatum.