A cyclophosphamide-resistant L1210 cell line has been shown to have unusually high aldehyde dehydrogenase activity. The sensitivity of this cell line to 4-methylcyclophosphamide and phosphoramide mustard in vivo and corresponding sensitivities in vitro indicate that 4-hydroxycyclophosphamide and/or aldophosphamide is the form in which cyclophosphamide reaches these tumor cells in mice and that intracellular aldehyde dehydrogenase activity is an important determinant of cyclophosphamide sensitivity in these leukemia cell lines.