Efficacy of liposomal as compared with free ampicillin in treatment of infection due to Listeria monocytogenes was studied in normal and congenitally athymic (nude) mice. After intravenous injection the multilamellar vesicles used were taken up mainly by liver and spleen, the target organs of L. monocytogenes. Injection of empty liposomes in two doses of 2 mumol of vesicle lipid each, administered at 40 and 112 hr after bacterial inoculation, did not influence the course of listerial infection in normal and nude mice. In normal mice liposomal entrapment of ampicillin resulted in significant improvement in the antibiotic's therapeutic index. The use of liposomal ampicillin at a total dose of 0.54 mg (two doses of 0.27 mg each) resulted in a therapeutic effect similar to that resulting from a total dose of 48 mg of free ampicillin (eight doses of 6 mg each). However, neither ampicillin treatment schedules cured infections in nude mice.