The anatomical distribution of serotonin-2 receptors in the human brain was studied by light microscopic autoradiography, using [3H]ketanserin as a ligand. The receptor densities were quantified by microdensitometry with the aid of a computer-assisted image-analysis system. A heterogeneous distribution of serotonin-2 receptor densities was found in the human brain. Very high concentrations were localized over layers III and V of several cortical areas, including the frontal, parietal, temporal and occipital lobes, the anterogenual cortex and the entorhinal area, as well as in the corpus mamillare of the hypothalamus. The claustrum, nucleus lateralis of the amygdala and some cortical layers also presented a high density of serotonin-2 receptors. Intermediate concentrations were found over the hippocampus, the caudatus, putamen and accumbens nuclei, and some nuclei of the amygdala, among other structures. Areas such as the thalamus, brain stem, cerebellum and spinal cord contained, in general, only low to very low densities of serotonin-2 receptors. A very high level of non-specific binding, which was not displaceable by any serotonin-2 compound, was found in some areas of the human brain, including the caudatus and putamen nuclei, the substantia nigra and the raphé nuclei. The distribution of serotonin-2 receptors in the human brain described herein is discussed in relation to the distribution of serotonergic innervation, the central effects which have been proposed to be serotonin-2-mediated, and the neuropathological characteristics of the diseases where a modification in the number of serotonin-2 receptors has been reported.