Two kinds of human tumor cell strains having different activity of O6-methylguanine-DNA methyltransferase (O6-MT) were transplanted into nude mice. Mice were then injected intraperitoneally (i.p.) with the bifunctional agent 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride(ACNU). The tumors with low O6-MT activity were quickly suppressed or cured. This result suggests that some tumors, if determined to have low O6-MT activity, might be cured if the host is treated with ACNU. This observation may open a new approach to experimental cancer chemotherapy. Treatment with ACNU of experimental animals bearing HeLaMR tumors (which have low O6-MT activity and are Mer-), resulted in the regression of the tumors or their disappearance. In animals bearing HeLaS3 tumors (which have high O6-MT activity and are Mer+) the tumors were hyperplastic.