Conventional preparations of amphotericin B (AmB) at established therapeutic doses are known to increase nonspecific immune responses. It remains to be established whether higher doses of the less toxic liposomal preparation of AmB maintains a beneficial effect on the immune response to fungal infections. Examination of the effect of treatment of human peripheral blood mononuclear cells from healthy subjects with various doses of both liposomal AmB (L-AmB) and deoxycholate AmB (d-AmB) on proliferation, cell viability, and percentage of apoptosis demonstrated that, although both L-AmB and d-AmB at low doses significantly increased nonspecific proliferative responses, L-AmB, but not d-AmB, treatment maintained this beneficial effect at higher doses. High doses of d-AmB, but not L-AmB, resulted in significantly decreased cell viability and increased apoptosis. This study provides further evidence in healthy human subjects for choosing L-AmB over conventional preparations in the clinical treatment of fungal infections requiring systemic high-dose treatment with AmB.