The topography of afferent projections to the mediodorsal thalamic nucleus of the rat has been studied using the retrograde transport of unconjugated wheat germ agglutinin as identified by immunocytochemistry. Inputs were defined according to the lateral, central or medial segments of the nucleus injected, and controlled by additional injections into the habenula, central medial and paraventricular nuclei of the thalamus. Cortical afferents to the lateral segment arose from anterior cingulate and prelimbic areas on the medial surface of the hemisphere, those to the central segment arose mainly from ventral orbital area, whilst those to the medial segment arose from the infra-limbic and agranular insular areas. This strict cortical topography was matched by the organization of afferents from the reticular thalamic nucleus; i.e. lateral, intermediate and medial reticular neurons from the rostral nucleus projected to lateral, central and medial segments of the mediodorsal thalamus respectively. In the basal forebrain ventral pallidum projected only to the medial segment, whilst magnocellular preoptic region projected only to the central segment. Lateral preoptic area projected to lateral and central segments and the diagonal band mainly to central segment. Projections from substantia innominata were found regardless of the area of mediodorsal nucleus injected. The paraventricular nucleus of thalamus, lateral habenula and substantia nigra reticulata projected to the lateral segment only, whilst central gray projected only to the medial segment. Projections from amygdala (mainly basolateral and central nucleus) were found only following central and medial segment injections. All regions of the mediodorsal nucleus injected received input from the lateral hypothalamus, the ventral tegmental area and the dorsal tegmental gray. The results are discussed and particular emphasis is placed on the possible functions of the thalamocortical connections and the role of the reticular thalamic nucleus as a potential regulator of thalamocortical activity.