Objective: To evaluate the effects of sleep on partial seizures arising from various brain regions. Methods: The authors prospectively studied 133 patients with localization-related epilepsy undergoing video-EEG monitoring over a 2-year period. Seizure type, site of onset, sleep/wake state at onset, duration, and epilepsy syndrome diagnosis were recorded. Periorbital, chin EMG, and scalp/sphenoidal electrodes were used. A subset of 34 patients underwent all-night polysomnography with scoring of sleep stages. Results: The authors analyzed 613 seizures in 133 patients. Forty-three percent (264 of 613) of all partial seizures began during sleep. Sleep seizures began during stages 1 (23%) and 2 (68%) but were rare in slow-wave sleep; no seizures occurred during REM sleep. Temporal lobe complex partial seizures were more likely to secondarily generalize during sleep (31%) than during wakefulness (15%), but frontal lobe seizures were less likely to secondarily generalize during sleep (10% versus 26%; p < 0.005). Conclusions: Partial-onset seizures occur frequently during NREM sleep, especially stage 2 sleep. Frontal lobe seizures are most likely to occur during sleep. Patients with temporal lobe seizures have intermediate sleep seizure rates, and patients with seizures arising from the occipital or parietal lobes have rare sleep-onset seizures. Sleep, particularly stage 2 sleep, promotes secondary generalization of temporal and occipitoparietal, but not frontal, seizures. These findings suggest that the hypersynchrony of sleep facilitates both initiation and propagation of partial seizures, and that effects of sleep depend in part on the location of the epileptic focus.