DBA/2 mice implanted i.p. with an aclarubicin (ACR)-resistant subline of L5178Y cells survived 4- to 5-fold longer than those with the parental cells; and animals with the Adriamycin- or bleomycin-resistant subline displayed an intermediate survival period. The i.p. treatment of mice with cyclophosphamide markedly enhanced i.p. growth of the ACR-resistant cells, suggesting that a certain host defense mechanism participates in the lower transplantability. In vitro, the ACR-resistant subline showed much higher sensitivity to natural killer cells. The i.p. pretreatment with anti-asialo-GM1 antibody markedly reduced the mean survival period of mice implanted i.p. with the ACR-resistant cells, suggesting that natural killer cells play an important role in the defense against transplantation of the ACR-resistant cells.