This study examines the effect of castration and androgen replacement on [125I]MK801 binding in the hippocampus. In castrated male rats, [125I]MK801 binding was significantly increased in both the stratum oriens and radiatum and the pyramidal cell layer of CA1. In contrast, no increase in [125I]MK801 binding was observed in the stratum oriens and radiatum of CA1 of castrated rats that were treated with dihydrotestosterone. No change in [125I]MK801 binding was observed in the CA3 region or dentate gyrus after castration. The observed increase in [125I]MK801 binding in pyramidal cell neurons within CA1 suggests that androgens may potentially affect hippocampal function by modulating pyramidal cell NMDA receptors.