Abstract: The combined effect of 1,2:5,6-dianhydrogalactitol (DAG) and vincristine (VCR) on L₁₂₁₀ leukemia was studied. The results obtaned in vivo suggest that simultaneous administration of DAG and VCR, or administration of these two agents within a 24 h interval, independent of order, produced a synergistic effect. The degree of synergism was dependent on dose and schedule. When DAG was given before VCR, the effect was more than the other two schedules of combination, Studies using different doses of DAG and VCR with an optimum schedule indicated that the degree of synergism was mainly dependent on the dose of DAG. When a dose of 3.0 mg/kg of DAG was given before 1.3 mg/kg of VCR within a 24 h interval, the survival time of the L₁₂₁₀-bearing mice was four times as long as additive, but the cell killing effect of the combination on the bone marrow stem cells was only increased by 12% over the additive. The schedule-dependent synergism for L₁₂₁₀ cells was also studied by the agar-diffusion-chamber assay.