The topographic distribution and density of the dopamine innervation in adult rat cerebral cortex were investigated by means of a recently improved radioautographic procedure for the light microscopic visualization and counting of monoamine axonal varicosities. Dopamine terminals were specifically labeled by high-affinity uptake in whole cerebral hemisphere slices incubated for 15 min at 35 degrees C with 10(-6) M tritiated dopamine in the presence of 10(-4) M pargyline and 5 X 10(-6) M desipramine. The slices were subsequently fixed, embedded in Epon and processed for light microscope radioautography as large 4-micron-thick (whole hemisphere) or smaller, semi-thin sections (selected areas). In radioautographs of serial semi-thin sections exposed for various periods of time, the number of labeled axonal varicosities reached a plateau after 12-14 days of exposure. Counts on such sections of increasing thickness allowed to calculate a correcting factor to transform numbers obtained from 4-micron-thick sections into their equivalent for a tissue thickness of 0.5 micron from which all varicosities were detected. The number of labeled varicosities could then be expressed per mm3 of tissue after measuring their mean caliper diameter in electron microscope radioautographs. As visualized at 3 transverse levels representing most of the major cytoarchitectonic divisions of cerebral cortex, two novel aspects were recognized in the topographic distribution of dopamine terminal: (1) the presence of a dopamine innervation in layer VIb of the frontal, parietal, temporal and occipital neocortex, and (2) a significant contingent of dopamine varicosities within the deep and not only upper layers of supragenual cingulate cortex. A fair number of dopamine varicosities were also detected in the upper layers of the dorsomedial frontal area, in the retrosplenial and adjacent occipital cortex as well as in the ventral subiculum and field CAl of the hippocampus. As measured in 10 sectors representing different cortical regions, the highest density of dopamine innervation was found in the supragenual cingulate cortex (1.7 X 10(6] and particularly in its layers II and III (3.1 X 10(6)). A slightly lower density was measured in the anteromedian "prefrontal" cortex (1.0 X 10(6)). The rostrorhinal and the perirhinal cortex showed moderate dopamine innervation (3.0 and 5.5 X 10(5)) with varicosities in every layer. The piriform and the posterior entorhinal cortex were also moderately and ubiquitously innervated (2.5 and 3.0 X 10(5)).(ABSTRACT TRUNCATED AT 400 WORDS)