The mediodorsal nucleus of the thalamus is an important component of the brain's circuitry for memory 9,20 and yet surprisingly little is known of its intrinsic organization. In the present study we have examined the distribution, spatial relationships and morphology of gamma-aminobutyric acid (GABA)-containing cells within the magnocellular and parvocellular subdivisions of the mediodorsal nucleus. These subdivisions have anatomically and functionally distinct connections with the orbital (limbic) and dorsolateral (association) areas of the prefrontal cortex, and accordingly, we investigated whether there were corresponding differences in their local circuit organization. Our findings show that round or ovoid GABA-immunoreactive neurons were abundant in both subdivisions. However, these neurons were larger in diameter in the magnocellular aspect (mean diameter = 10.4 +/- 0.1 micron) than in the parvocellular moiety (mean diameter = 9.9 +/- 0.1 micron) and the intensity of reactivity was also greater for the magnocellular neurons. Comparison of the densities of GABA-immunoreactive neurons revealed not only a greater density of neurons in the parvocellular division but also that the proportion of all neurons which were GABA-containing was greater in this region. These differences in the morphology and density of inhibitory local circuit neurons may contribute to the functional duality of prefrontal cortex innervated by these thalamo-cortical pathways. Certain qualitative features were common to both subdivisions; thus GABA-immunoreactive neurons were found in small clusters throughout the magnocellular and parvocellular divisions of the mediodorsal nucleus and, in addition, regions with few or no GABA-immunoreactive cells were often surrounded by strings of GABA-containing neurons.(ABSTRACT TRUNCATED AT 250 WORDS)