Hippocampal long-term depression (LTD) comprises a persistent decrease in synaptic transmission which is induced by repeated low-frequency stimulation (LFS). Although LTD has been widely demonstrated in the CA1 region in vitro, very few positive reports of LTD in vivo have occurred. In this study, the conditions under which homosynaptic LTD occurs in the CA1 region of freely moving rats was investigated. Three rat strains were studied: Wistar, Sprague-Dawley and Hooded Lister. Whereas Wistar and Sprague-Dawley rats expressed optimal LTD following 1 Hz LFS, Hooded Lister rats showed no LTD when tested in an LFS range of 1-10 Hz. Exposure to marked stress transiently enhanced LTD obtained in Wistar and Sprague-Dawley rats, but did not facilitate LTD induction in the LTD-resistant strain. It was possible to induce long-term potentiation with high-frequency stimulation, although the profile of LTP was different in each strain. These data suggest that the expression of LTD varies according to the strain of rat used and is tightly dependent upon stimulation frequency. In addition the behavioral state of the animal may influence LTD expression. These data may explain, in part, the conflicting reports with regard to the inducibility of hippocampal LTD in vivo.