Summary:Epileptic mechanisms in the brain are subject to long‐duration, time‐ordered neuromodulatory processes controlled by endogenous oscillators which are responsible for appropriately phased modulation of various normal physiological processes, including the 24‐h sleep/wakefulness cycle and the ultradian 100‐min cycle of rapid eye movement/non‐rapid eye movement sleep. Both focal and generalized types of epileptiform activity in humans are subject to biorhythmic modulation, and the various modulation patterns observed are in accord with a model which explains these patterns as a consequence of the interaction of two endogenous modulatory processes: one with a period of about 24 h, the other with a period of about 100 min. Differences in the phase angle between the two cyclic processes, determined by time of sleep onset, explain the various modulatory patterns observed. The mechanisms involved in the genesis and elaboration of electrical epileptiform activity in animal models are examined in relation to known processes involved in the physiology of sleep, and compared with data derived from long‐term studies of the time distribution of epileptic events in humans. In infantile spasms, clinical seizure activity and the ictal and interictal EEG patterns in relationship to the phases of the sleep cycle, the significant defects in the quality and quantity of sleep in this disorder, and the changes that take place in all of these when seizures are abolished by effective treatment, suggest that pontine mechanisms responsible for the sleep cycle may be involved in the elaboration of infantile spasms and hyp