Density of synaptic profiles in layer 3 of middle frontal gyrus was quantitated in 21 normal human brains ranging from newborn to age 90 years. Synaptic profiles could be reliably demonstrated by the phosphotungstic acid method (Bloom and Aghajanian) in tissue fixed up to 36 h postmortem. Synaptic density was constant throughout adult life (ages 16--72 years) with a mean of 11.05 X 10(8) synapses/cu.mm +/- 0.41 S.E.M. There was a slight decline in synaptic density in brains of the aged (ages 74--90 years) with a mean of 9.56 X 10(8) synapses/cu.mm +/- 0.28 S.E.M. in 4 samples (P less than 0.05). Synaptic density in neonatal brains was already high--in the range seen in adults. However, synaptic morphology differed; immature profiles had an irregular presynaptic dense band instead of the separate presynaptic projections seen in mature synapses. Synaptic density increased during infancy, reaching a maximum at age 1--2 years which was about 50% above the adult mean. The decline in synaptic density observed between ages 2--16 years was accompanied by a slight decrease in neuronal density. Human cerebral cortex is one of a number of neuronal systems in which loss of neurons and synapses appears to occur as a late developmental event.