Summary: Infraslow activity (ISA), direct coupled (DC), and direct current (DC) are the terms used to describe brain activity that occurs in frequencies below 0.1 Hz. Infraslow activity amplitude increase is also associated with epilepsy, traumatic brain injuries, strokes, tumors, and migraines and has been studied since the early 90s at the Henry Ford Hospital MEG Laboratory. We have used a DC-based magnetoencephalography (MEG) system to validate and characterize the ISA from animal models of cortical spreading depression thought to be the underlying mechanism of migraine and other cortical spreading depression–like events seen during ischemia, anoxia, and epilepsy. Magnetoencephalography characterizes these slow shifts easier than electroencephalography because there is no attenuation of these signals by the skull. In the current study, we report on ISA MEG signals of 12 patients with epilepsy in the preictal and postictal states. In the minutes just before the onset of a seizure, large-amplitude ISA MEG waveforms were detected, signaling the onset of the seizure. It is suggested that MEG assessment of ISA, in addition to activity in the conventional frequency band, can at times be useful in the lateralization of epileptic seizures.