Muramyl dipeptide (MDP), a part of bacterial cell wall peptidoglycans, was active as adjuvant and stimulated the reticuloendothelial system (RES) of mice to increase its phagocytic function. A series of analogs of MDP was tested for their adjuvant activity and RES-stimulating activity. Sex differences were observed in the adjuvant activity and RES-stimulating capacity of some MDP analogs. A stereochemically highly specific structure required for MDP to exert adjuvant activity was also required for its RES-stimulating activity. Based on this close correlation among the structure, adjuvant activity, and RES-stimulating capacity of MDP, we infer that macrophages may play an important role in the expression of adjuvant activity of MDP.