Cortical and subcortical afferents to the cat's thalamic mediodorsal nucleus (MD) were investigated using the method of retrograde transport of horseradish peroxidase (HRP). HRP was applied using vertical or oblique approaches and either a microsyringe or implanted pipettes filled with HRP-powder. A wide variety of cortical afferents to MD was detected: Aside from afferents from the cat's classical prefrontal cortex (gyri proreus, rectus, frontalis), from adjacent areas of the premotor and cingulate cortex and from portions of the insular cortex, afferents were found from cortical areas related to the processing of somatosensory, gustatory, auditory and visual information and from portions of the parietal and temporal association cortex. A considerable number of afferents arose from the diagonal band of Broca and a small number from the precommissural septum, periamygdaloid , prepiriform , entorhinal, subicular and amygdalar regions. The preoptic region and hypothalamic areas contained some labeled cells. All brains, with the exception of one with a very small dorsomedial injection, contained labeled cells in the mamillary bodies. The reticular nuclear complex and the ventral lateral geniculate nucleus were the main sources of afferents on the thalamic level. In the brain stem the substantia nigra, the ventral tegmental area, the deep layers of the superior colliculus, pretectal and tegmental regions contained labeled cells. These results show that MD receives afferents from a large variety of structures. Among them are several cortical as well as subcortical regions related to the processing of sensory and motor information. Taken together, these connections and the numerous afferents to MD from regions related to emotional and motivational behavior confirm the view that MD has to be termed association nucleus.