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The synthesis and biological activity of new conjugates of muramyl dipeptide (MDP) and nor-muramyl dipeptide (nor-MDP) with tuftsin and retro-tuftsin derivatives containing isopeptide bond between ε-amino group of lysine and carboxyl group of simple amino acids such as Ala, Gly and Val are presented. We presumed, based on the cytokine profile, that the examined conjugates of tuftsin and MDP were capable of activating antibacterial mechanisms by switching on Th1 immune response. The most active were compounds 11, 14 and 19-23.