Autoradiographic analysis of 5-HT2 receptors in the human brain, using [3H]ketanserin as a ligand, reveals region-specific changes in receptor labeling as a function of age. In the prefrontal cortex and hippocampal dentate gyrus of 12 normal subjects, label density decreases sharply with age over the 2nd and 3rd decades, reaches a minimum around age 50 and then starts to increase again in the 6th and 7th decades. Other brain regions studied, including frontoparietal and temporal cortex, basal ganglia and thalamus, did not show significant changes with age. Saturation binding experiments on prefrontal cortical samples from 23 normal subjects reveal that the decrease in label density is due to changes in receptor density (Bmax) with no apparent change in affinity (Kd). Sex, presence of alcohol and postmortem delay had no effect on ketanserin binding.