Summary: We analyzed the frequency and morphological characteristics of the initial EEG manifestations of spontaneous seizures recorded from depth and subdural electrodes in 26patients for whom pathological analysis of the area of seizure onset was available after resective surgery. Pathological features considered to be positive findings included well-defined structural lesions (hamartoma, neoplasm) or strictly defined mesial temporal sclerosis. Seizure onset was characterized by the frequency of the rhythmic discharge >2 Hz in the first second and by the presence or absence of periodic low-frequency spikes (<2 Hz) preceding this stable change in background frequency. These features were correlated with the presence or absence of pathologic abnormalities in temporal and extratemporal locations. Although all patterns and frequencies of seizure onset were recorded in both medial temporal and extratemporal locations, medial temporal seizure onset was significantly more likely to have high frequency (>13 Hz, p < 0.05) and no periodic spikes before seizure onset tended to periodic spikes prior to the seizure when it was associated with medial temporal sclerosis compared to when it was not. Extratemporal seizure onset associated with abnormal pathological substrate was significantly more likely to have a lower frequency (<13 Hz, p < 0.05) and no periodic spikes before seizure onset (p < 0.00001) than extratemporal seizure onset recorded from areas without pathological findings. Variability of seizure onset frequency was a characteristic of temporal, but not extra temporal, seizures (p < 0.01). The existence of such differences between seizures of temporal and extratemporal origin suggests that the underlying anatomy may in part determine these patterns, and that interpretation of EEG records of seizures beginning in different cerebral locations requires recognition of these differences.