From June 1983 to January 1994, 22 adult patients with severe Listeria monocytogenes meningoencephalitis were observed in our Intensive Care Unit. Listeria monocytogenes was obtained in culture in cerebrospinal fluid or blood for every patient. Seven patients were treated with the combination ampicillin-aminoglycoside (group A) and 15 patients with the combination ampicillin (or amoxicillin)-cotrimoxazole (group A + C). Risk factors and gravity scores were similar in both groups. Failure of the 'gold standard' regimen (group A) was significantly higher (57%) compared to group A + C (6.7%) (P < 0.05). Mortality related to L. monocytogenes was 23.5% in group A compared to 6.7% in group A + C. Morbidity was reduced in group A + C (13.3%) compared to group A (60%) (P = 0.15). This unique study seems to demonstrate that amoxicillin-cotrimoxazole should be the most appropriate therapeutic regimen for Listeria meningoencephalitis.