Powerful endogenous inhibitory mechanisms are thought to restrict the spread of epileptic discharges in cortical networks. Similar inhibitory mechanisms also influence physiological processing. We reasoned, therefore, that useful information about the quality of inhibitory restraint in individuals with epilepsy may be gleaned from psychophysical assays of these physiological processes. We derived a psychophysical measure of cortical inhibition, the motion surround suppression index (SSI), in 54 patients with epilepsy and 146 control subjects. Multivariate regression analyses showed that SSI was predicted strongly by age and seizure type, but not by seizure frequency. Specifically, we found that patients with exclusively focal epilepsy, and no history of generalization, showed significantly stronger cortical inhibition as measured by the SSI compared to all other groups, including controls. In contrast, patients with focal seizures evolving into generalized seizures, and patients with generalized genetic epilepsy, showed similar levels of cortical inhibition to controls. The presumptive focus, when one could be identified, was rarely found in visual cortex, meaning that the relationship with the epilepsy subtype is likely to reflect some global difference in inhibition in these subjects. This is the first reported instance of raised SSI in any patient cohort, and appears to differentiate between patients with respect to the likelihood of their experiencing generalization of their seizures. These results suggest that such simple psychophysical assays may provide useful aids to clinical management, particularly at the time of diagnosis.