Abstract The ability of N-acetylmuramyl- l-alanyl- d-isoglutamine (MDP) and its adjuvant-inactive stereoisomer, N-acetylmuramyl- d-alanyl- d-isoglutamine, (MDP(D-D)) to inhibit the in vitro growth of 3 murine ascitic thymoma lines, expressing different Lyt-phenotypes, was studied. MDP inhibited the growth of all 3 cell lines. MDP(D-D) inhibited the 2 cell lines expressing Lyt-1 +2 − or Lyt-1 +2 + phenotypes, but not the third cell line which expressed the Lyt-1 −2 + phenotype. The ability of MDP or MDP(D-D) to inhibit thymoma growth was lost when the ascitic cell populations were depleted of macrophages. MDP could be replaced by a supernatant derived from an ascitic Lyt-1 +2 − cell population exposed to MDP. The supernatant required the presence of macrophages for activity. The inhibition by MDP of the growth of the Lyt-1 −2 + cell line was prostaglandin synthetase dependent: indomethacin antagonized the inhibitory activity of MDP. The inhibition by MDP of the Lyt-1 +2 − cell line was partially antagonized by indomethacin, and no antagonism was observed with the Lyt-1 +2 + cell line.