A lipophilic derivative of muramyl dipeptide, muramyl tripeptide cholesterol, was incorporated into poly(D,L-lactide) nanocapsules and its immunomodulating properties were assessed in vitro. The nanocapsule form was more effective than the free drug in activating rat alveolar macrophages for a cytostatic effect toward syngeneic tumor cells. Induction of NO synthase correlated with anti-proliferative activity. The time course of activation and the effect of inhibitors of endocytosis suggested that this increased efficiency was due to improved intracellular delivery by phagocytosis of nanocapsules. Such nanocapsules might be useful for immunotherapy of metastases resistant to conventional treatment, since they could overcome two problems associated with soluble muramyl peptides: rapid elimination and poor uptake by macrophages.