In recent years, Creutzfeldt-Jakob disease (CJD) has been supposed to be of viral origin, and amantadine hydrochloride has been suggested as therapy because of its proved antiviral action. We studied nine patients with CJD (confirmed at autopsy in seven). Four were treated with amantadine hydrochloride, in dosages ranging from 3.5 to 15 mg/kg/day for an average period of 32 days. The clinical evolution of their disease was compared with that in five patients receiving only supportive maintenance therapy. The length of survival from the onset of clinical care did not differ significantly between the two groups. Nevertheless, a transient improvement in wakefulness and mentation was observed in three patients treated with amantadine, and EEG changes were observed in two, consisting above all of a reduction in the slow-wave activity and the periodic discharges (PDs). Amantadine administered intravenously did not induce any short-term changes in the PDs or the cyclic alternating pattern.