The therapeutic efficacy of three lipid formulations of amphotericin B was compared with that of conventional amphotericin B in treatment of murine coccidioidomycosis. All treatments prolonged survival compared with the no-treatment group (P < 0.0001). Although conventional amphotericin B was more active than lipid formulations on reducing quantitative fungal load on a milligram-per-kilogram basis (P < 0.003 to 0.0002), the lipid preparations could be administered at higher doses, sterilizing liver and spleen tissues. The efficacies of the lipid preparations were similar in this murine model of coccidioidomycosis.