The specific binding of 125I-Tyr11-somatostatin-14 (125I-Tyr11-SS-14) was measured in different cortical regions after unilateral ibotenic acid lesion of the rat nucleus basalis magnocellularis (NBM). A marked loss of acetylcholinesterase-positive fibers was observed in the frontal, parietal, temporal and occipital cortices ipsilateral to the lesion. The loss of cholinergic cell bodies in the NBM was further investigated with choline-acetyltransferase (ChAT) immunohistochemistry which indeed demonstrated a loss of ChAT-positive magnocellular perikarya. Autoradiographic analyses of specific binding of 125I-Tyr11-SS-14 demonstrated a significant reduction in binding density in the denervated parts of the neocortex. The decrease in specific binding was most pronounced (40-50%) in the superficial layers (I-III) of the frontal, parietal and temporal cortices 2 and 4 weeks after lesion. A significant loss in 125I-Tyr11-SS-14 binding in the deeper layers was only observed in the frontal cortex after 2 and 4 weeks. In the occipital cortex a significant decrease was measured in the superficial layers only after 4 weeks. The specific binding in all cortical regions returned to normal after 6 weeks. The results suggested that 125I-Tyr11-SS-14 binding sites are localized on cholinergic afferents in the rat neocortex and that an up-regulation of number of binding sites, alternatively an increased binding affinity occurred with time after lesion.