In an attempt to evaluate the cellular organization and efferent projections of the nucleus tegmenti pedunculopontinus pars compacta, several experiments were performed in the rat. From measurements of neurons in the nucleus tegmenti pedunculopontinus pars compacta in Nissl-stained sections, the nucleus was observed to contain many large neurons which made it possible to demarcate this nucleus from surrounding pontomesencephalic reticular formation. Two other neuronal populations, medium and small neurons, were also seen in the nucleus tegmenti pedunculopontinus pars compacta. Detailed measurements showed that 90% by volume of all neurons in the nucleus tegmenti pedunculopontinus pars compacta were large and medium-sized neurons. After injections of [3]leucine into the nucleus tegmenti pedunculopontinus pars compacta, transported label was observed in dorsally and ventrally coursing ascending fibers. The dorsally coursing fibers entered the centrolateral nucleus and centre median-parafascicular complex of the thalamus. The ventrally coursing fibers produced accumulation of silver grains in the ventral tegmental area, substantia nigra pars compacta, subthalamic nucleus, zona incerta and lateral hypothalamus. Crossed fibers of the nucleus tegmenti pedunculopontinus pars compacta were observed sparsely at the levels of the thalamus and posterior commissure, and to a greater degree through the supraoptic commissure of Meynert. Much less anterograde labeling was seen in the equivalent terminal sites on the contralateral side of the brain. By electron microscopic autoradiography major terminal sites of axons of the nucleus tegmenti pedunculopontinus pars compacta were examined in rats injected with [3H]leucine in the nucleus tegmenti pedunculopontinus pars compacta and later injected with horseradish peroxidase in the striatum and pallidum. Statistical data showed preferential radiolabeling of terminals forming asymmetrical synaptic contact with dendrites in the centrolateral nucleus, centre median-parafascicular complex and subthalamic nucleus. Apparent terminations in the substantia nigra pars compacta proposed in earlier studies and shown in the present light microscopic autoradiograms were not supported by this ultrastructural analysis. Several radiolabeled terminals of the asymmetrical type contacting horseradish peroxidase labeled dendrites in the thalamus confirmed direct input from the nucleus tegmenti pedunculopontinus pars compacta to the thalamostriate projection neurons. [3H]choline injections into the thalamus and subthalamic nucleus produced retrograde perikaryal labeling of large neurons in the nucleus tegmenti pedunculopontinus pars compacta.