An average of 15-20% of patients on the ketogenic diet (KD) experience a >50% reduction in seizure frequency; however, 10-40% discontinue the diet due to either a lack of response or adverse side effects. This variability in patient response raises the possibility that genetic factors may influence the efficacy of the KD. As a first step towards identifying these factors, we evaluated the ability of the KD to alter seizure thresholds in four commonly used inbred mouse strains: C57BL/6J, FVB/NJ, A/J, and DBA/2J. We observed strain-specific differences, indicating that genetic factors are likely to influence efficacy.