Objective: To investigate whether Unverricht-Lundborg disease (ULD) and Laf ora body disease (LBD) can be differentiated on the basis of their neurophysiolo gic profiles. Methods: Somatosensory evoked potentials (SSEPs), long-loop refl exes (LLRs), and the influence of conditioning nerve stimulation on the motor po tentials evoked by transcranial stimulation in 8 patients with LBD and 10 patien ts with ULD were investigated. Results: Both groups showed sensorimotor cortex h yperexcitability, but their electrophysiologic profiles were different. Enlarged P25 to N33 SSEP components and enhanced LLRs were common in the ULD patients, w hereas medium-latency “ giant” SSEP components and less consistently enhanc ed LLRs were more frequently found in the patients with LBD. Cortical relay time was extremely brief in ULD but varied in LBD. Conditioning somatosensory stimul i differently affected motor cortex excitability, leading to early facilitation in ULD and delayed and prolonged facilitation in LBD. Conclusions: Patients with Unverricht-Lundborg disease (ULD) and Lafora body disease (LBD) have differen t electrophysiologic profiles. The ULD findings point to an aberrant subcortical or cortical loop (possibly short-cutting the somatosensory cortex) that is in volved in generating the prominent action myoclonus characterizing the disorder. The LBD findings highlight sustained hyperexcitability of the sensorimotor cort ex in response to afferent stimuli, which fit with a more severe impairment of i nhibitory mechanisms. Objective: To investigate whether Unverricht-Lundborg disease (ULD) and Lafra body disease (LBD) can be differentiated on the basis of their neurophysiolo gic profiles. Methods: Somatosensory evoked potentials (SSEPs), long-loop refl exes and the influence of conditioning nerve stimulation on the motor po tentials evoked by transcranial stimulation in 8 patients with LBD and 10 patien ts with ULD were investigated. Results: Both groups showed sensorimotor cortex h yperexcitability, but their electrophysiologic profiles were different. Enlarged P25 to N33 SSEP components and enhanced LLRs were common in the ULD patients, w hereas medium-latency “giant” SSEP components and less consistently enhanc ed LLRs were more frequently found in the patients with LBD. Cortical relay time was extremely brief in ULD but varied in LBD. Conditioning somatosensory stimul i differently affected motor cortex excitability, leading to early facilitation in ULD and delayed and prolonged facili tation in LBD. Conclusions: Patients with Unverricht-Lundborg disease (ULD) and Lafora body disease (LBD) have differen t electrophysiologic profiles. The ULD findings point to an aberrant subcortical or cortical loop (possibly short-cutting the somatosensory cortex) that is in volved in generating the prominent action myoclonus characterizing the disorder. The LBD status highlight sustained hyperexcitability of the sensorimotor cort ex in response to afferent stimuli, which fit with a more severe impairment of ihibitory mechanisms.