The purpose was to study homosynaptic long-term depression (LTD) at the parallel fiber-Purkinje cell synapse in the mdx mouse, a murine model of the human dystrophinopathy, Duchenne muscular dystrophy (DMD), in order to examine whether the absence of dystrophin affects the induction and extent of this form of synaptic plasticity. Sharp intracellular electrodes were used to record electrically evoked excitatory postsynaptic potentials (EPSPs) from identified Purkinje cells in cerebellar slices. The early phase of homosynaptic LTD, 7-16 min postinduction, was the same in mdx and wildtype Purkinje cells; however, the late phase of LTD, 35-44 min, was significantly enhanced in mdx Purkinje cells. We hypothesize that this enhancement of the late phase of homosynaptic LTD may be due to a disruption of Ca(2+) homeostasis associated with the absence of the protein dystrophin. These findings may explain some of the central nervous system deficiencies reported in DMD boys.