The failure of chemotherapy often results in the outgrowth of drug-resistant tumor cells, and, since chemotherapy is often combined with immunotherapy, the question arises as to whether immunity directed against the original tumor offers any protection against the drug-resistant tumor cells. To approach this problem, the immunological relationships between a mouse glioma (GL26) and two FUdR-resistant transplantable tumor sublines were studied. Immunity was induced in C57BL/6 mice with neuraminidase-altered GL26 tumor cells. Immunized mice challenged with viable GL26 tumor cells were completely protected, and no tumors grew. Immune mice, when rechallenged with cells from the two FUdR-resistant tumors, gave greater protection against one of the tumors than the other, but not as much as against the original tumor. The results indicate the drug-resistant tumor cells have some immunological properties similar to the original tumor line and that further studies such as these might be of value to the staging of chemoimmunotherapy.