Epileptiform abnormalities often occur at specific times of day or night, possibly attributable to state of consciousness (sleep vs. wake) and/or influences from the endogenous circadian pacemaker. In this pilot study we tested for the existence of circadian variation of interictal epileptiform discharges (IEDs), independent of changes in state, environment, or behavior. Five patients with generalized epilepsy underwent a protocol whereby their sleep/wake schedule was evenly distributed across the circadian cycle while undergoing full-montage electroencephalography and hourly plasma melatonin measurements. Light was <8 lux to prevent circadian entrainment. All patients completed the protocol, testifying to its feasibility. All patients had normal circadian rhythmicity of plasma melatonin relative to their habitual sleep times. In the three patients with sufficient IEDs to assess variability, most IEDs occurred during non-rapid eye movement (NREM) sleep (ratio NREM:wake=14:1, P<0.001). In both patients who had NREM at all circadian phases, there was apparent circadian variation in IEDs but with different phases relative to peak melatonin.