Comined chemotherapy approaches should take into account the complex interrelationships with the host and tumor. Principles of combination drug chemotherapy that may contribute to increased antitumor specificity in the treatment of clinical neoplasia are reviewed and examples provided under the following broad headings; (a) Increased antitumor effectiveness without a proportionate increase in limiting host toxicity. This includes the biochemical concepts of sequential and concurrent blockade, complementary inhibition and error amplification, (b) Decrease in host toxicity without a proportionate loss in antitumor effectiveness, (c) Delay in origin and treatment of resistant mutants, (d) Treatment of metastatic and sequestered tumor cells, (e) Identification of optimal dosages, ratios and schedules for drug combinations, (f) Kinetic considerations such as tumor cell synchronization, choice of drugs that act at different phases of the cell cycle or that stimulate Go cells to divide, (g) Use of drugs that assist active compounds, (h) Employment of combined modalities including surgery, radiation or immunotherapy plus chemotherapy, (i) Loading dose chemotherapy of advanced disseminated tumor, (j) Identification of drugs that may prevent viral or carcinogenic tumor induction, (k) Development of methodology for determination of the effectiveness of polychemotherapy.