An electroclinical mismatch is present if the electroencephalogram (EEG) shows evidence of moderate to severe diffuse encephalopathy but the patient's mental status is only mildly altered. We describe five cases in which seizure or status epilepticus was suspected due to electroclinical mismatch. In all five cases, EEG was ordered to rule out nonconvulsive status epilepticus as the cause of the altered mental status. EEG initially showed generalized delta activity (GDA), with variable degrees of rhythmicity, with or without superimposed theta activity, with or without sporadic epileptiform discharges. During EEG acquisition, all patients followed commands and answered questions. The mental status change was limited to mild inattention and temporal disorientation. Benzodiazepine challenge was performed by administering lorazepam 2-mg IV. Within 10 minutes of injection, GDA started to break up and subsequently disappeared. EEG showed prominent sleep spindles in three patients and background changes, indicating drowsiness in two patients. The assessment of clinical response to lorazepam was confounded by sleepiness in all patients. Serial EEG recording or continuous EEG monitoring revealed reemergence of GDA, at times appearing more rhythmic than the GDA in the baseline study. All patients received nonsedating antiseizure drugs. GDA completely resolved and mental status normalized two to five days after starting antiseizure medication. In cases of electroclinical mismatch, the absence of clear-cut epileptiform discharges does not exclude the possibility that cortical hyperexcitability is contributing to the encephalopathic process. A positive response to benzodiazepine challenge suggests the presence of cortical hyperexcitability and the need to start, or increase the dosage of, antiseizure drugs.