The effects of bifemelane hydrochloride on changes of N-methyl-D-aspartate receptors and muscarinic cholinergic receptors were examined in the gerbil hippocampus after transient ischemia with radioactive-specific ligands. There were marked reductions in both these receptors in the gerbil hippocampus 14 days after transient ischemia, without changes in the respective affinities. Post-ischemia bifemelane treatment almost completely prevented the ischemia-induced decreases in the numbers of these receptors, and had no effect in sham-operated controls. The results of the present study suggest that this drug prevents postsynaptic dysfunction induced by transient ischemia, and may be useful in the therapy of both the chronic and the acute stage of cerebrovascular disease.