Generalized periodic epileptiform discharges (GPEDs) are generalized, synchronous electrographic discharges. This study investigates etiologies, relationship to status epilepticus (SE), and the prognosis for patients with GPEDs. All EEGs with GPEDs performed at Duke University Medical Center between January 1994 and October 1995 were identified. Clinical histories and EEGs were reviewed. They were divided into groups depending on the etiology of the GPEDs, whether the patients were in SE or not, and whether they were alive or not at discharge. A comparison of histories and GPED characteristics among groups was undertaken using parametric and nonparametric t tests. Twenty-five patients were enrolled: 7 (28%) had toxic-metabolic encephalopathy, 10 (40%) had anoxia and toxic-metabolic encephalopathy, and 8 (32%) had a primary neurologic process. Eight patients (32%) were in SE. In the SE group, GPED amplitude was higher (110 versus 80 µV, P < 0.05), GPED duration was longer (0.5 versus 0.3 seconds, P < 0.05), and inter-GPED amplitude was higher (34 versus 17 µV, P < 0.05). Nine patients (36%) were alive at discharge; they were more likely to be younger (51 versus 68 years, P < 0.05), have a better mental status at the time of their EEG, and have a higher inter-GPED amplitude (33 versus 18 µV, P < 0.05). A variety of conditions, including SE, can cause GPEDs. Intergroup differences in historic and GPED features exist between those patients in SE and those not in SE and those with good and poor prognoses.