In the human neocortex, progressive synaptogenesis in early postnatal life is followed by a decline in synaptic density, then stability from adolescence until middle age. No comparable data are available in the hippocampus. In this study, the integral synaptic vesicle protein synaptophysin, measured immunoautoradiographically, was used as an index of synaptic terminal abundance in the hippocampal formation of 37 subjects from 5 weeks to 86 yr old, divided into 4 age groups (10 infants, 15 adolescents/young adults, 6 adults, and 6 elderly). In all hippocampal subfields, synaptophysin was lowest in infancy, but did not differ significantly between the older age groups, except in dentate gyrus (DG) where the rise was delayed until adulthood. A similar developmental profile was found in the rat hippocampus. We also measured synaptophysin mRNA in the human subjects and found no age-related changes, except in parahippocampal gyrus wherein the mRNA declined from infancy to adolescence, and again in old age. The synaptophysin protein data demonstrate a significant presynaptic component to human postnatal hippocampal development. In so far as synaptophysin abundance reflects synaptic density, the findings support an increase in hippocampal and parahippocampal synapse formation during early childhood, but provide no evidence for adolescent synaptic pruning. The mRNA data indicate that the maturational increases in synaptophysin protein are either translational rather than transcriptional in origin, or else are secondary to mRNA increases in neurons, the cell bodies of which lie outside the hippocampal formation.