Prior to the release of carbamazepine for the treatment of patients with psychomotor and grand mal seizures, primidone was regarded as the drug of choice for these disorders, especially when combined with diphenylhydantoin (DPH). It was, therefore, of interest to compare the effectiveness of carbamazepine against primidone when added to a therapeutic dose of DPH. Forty-five patients completed a 6-month study with each patient serving as his own control. The patients were initially stabilized on therapeutic doses of DPH and one of the test compounds, while all other medications were withdrawn. After 3 months of treatment, they were transferred onto the other drug for a second 3-month period. Extensive laboratory testing, including anticonvulsant levels, electroencephalograms, and neuropsychological evaluations, was performed. For the most part, the patients remained on outpatient status, returning for reports of seizure frequency, side effects, and laboratory studies every 14 days. The study was conducted in a single blind fashion by the treating neurologists; double blind by the electroencephalographer and psychologists. The results indicated that the two drugs did not differ in their effectiveness on seizure control. There were somewhat more side effects—none serious—with carbamazepine than with primidone. The EEG showed increased fast activity with primidone and increased &thetas; activity with carbamazepine. There was no difference in regard to decrease of electroencephalographic seizure discharges. The patients showed more impairment on a repeatable neuropsychological test battery with primidone than with carbamazepine, and they also showed an increase on the psychopathic deviate scale of the Minnesota Multiphasic Inventory. Depressive feelings, when present, lessened while under treatment with carbamazepine. The results suggest that patients with the seizure types under consideration and who do not respond to DPH alone or to a DPH-phenobarbital combination can be placed on either carbamazepine or primidone while phenobarbital is discontinued. A patient who is intellectually and emotionally intact with no past history of behavioral disturbances may do better on primidone than carbamazepine, because this drug gives fewer side effects. On the other hand, those patients who have a past history of emotional and/or intellectual disturbances may profit more from carbamazepine.