The long term consequences of graduated interference with the acquisition of hippocampal neurons and glia during early infancy were examined with quantitative histology and 3H-thymidine autoradiography. the head region containing the hippocampus was irradiated from day two on with either two (2X), four (4X), six (6X) or eight (8X) doses of 150-200r X-rays. The animals were killed at 30, 60, 90 and 120 days of age. The morphology of the hippocampus was normal in all irradiated groups with the characteristic interlocking flods of the pyramidal and granular layers. While the number of pyramidal calls of Ammon's horn was unaffected, the number of granule cells of the dentate gyrus was progressively and permanently reduced from control levels by the different dosage schedules (2X, 59% reduction; 4X, 77%; 6X, 83%; 8X, 84%). Incidental observations in control animals indicated a 20% increase in granule cells between 30 and 120 days of age in agreement with earlier observations of granule cell labelling after 3H-thymidine injections in adult rats. The time of origin of tha approximately 15-16% of the granule cells surviving irradiation in the 8X group was determined by injecting either pregnant females (gestation days 19-20) or pups (days 0 and 1) with two successive dosed of 3H-thymidine; the animals were irradiated from day two on the eight X-ray doses. The granule cells surviving in the postnatally injected group were all unlabelled and comparable in number to the unlabelled cells in control animals that were given five successive postnatal injections of 3H-thymidine. This established that the radioresistant complement of granule cells is formed prenatally. In the prenatally injected group, over half the surviving cells were labelled; it was assumed that those not labelled were formed befor gestation day 19. In contrast to the permanent reduction in the number of granule cells, there was some reestablishment of the number of cells in the dentate molecular layer and the Ammonic stratum oriens; in the fimbria, recovery in cell number was complete by 60 days. In a supplementary autoradiographic experiment, cell proliferation in the granular layer and in the fimbria was determined at 60 days of age after a single postnatal injection of 3H-thymidine on either day 15 or day 20 in the control, 2X, 4X and 6X groups. The number of labelled cells in the irradiated groups was always well below control levels in the granular layer, but it was wither above or at the same level as controls in the fimbria. Tentative interpretations were offered for the differential long-term effects of variable X-ray schedules on the neuronal and glial populationf of the hippocampus.