Twenty-six adults with severe progressive myoclonus epilepsy (PME) were admitted to a long-term prospective clinical study; 19 were followed up for six years. The previous medication, phenytoin sodium and other antiepileptic drugs, was changed to valproate sodium (Deprakine [Finland]; Depakene Syrup, comparable US product), clonazepam (Clonopin), and phenobarbital, and the patients' conditions improved. After six years of follow-up, the favorable result continued. The mean plasma concentration in 26 patients after four months of follow-up was 27.8 +/- 6.9 mg/L for valproate, 0.053 +/- 0.025 mg/L for clonazepam, and 19.2 +/- 7.9 mg/L for phenobarbital. The clinical response was not in accordance with the plasma drug concentrations when the data of the whole population were statistically analyzed. The classification of disability of patients with PME into five degrees was useful. The longlasting favorable result suggests that the combination of valproate, clonazepam, and phenobarbital is the most effective therapy for severe PME.