In a study population of 152 patients seen at Thomas Jefferson University Hospital's sickle cell center between 1981 and 1992, 21 patients with seizures were identified. Clinical charts, electroencephalograms and neuroradiological studies were reviewed retrospectively. Seventeen patients with epilepsy were identified. Eleven had generalized tonic-clonic, 2 had partial, and 4 had poorly characterized seizures. CT/MRI evaluation was focally abnormal in 6 patients, 4 of whom had cortical lesions. Atrophy was noted in 3 patients, while imaging studies were normal in 6 patients. The EEGs demonstrated focal epileptiform discharges in 9 patients, generalized slowing in 5 patients, and was normal in 3 patients. Four patients had generalized seizures only with meperidine administration, all of whom had nonfocal EEG and radiological studies. We concluded that (1) epilepsy is more common in sickle cell patients than in the general population; (2) the majority of our epileptic sickle cell patients have nonfocal CT or MRI studies but demonstrate focal EEG abnormalities; and (3) meperidine administration is associated with generalized seizures in sickle cell patients.