CPT-I I , 7-ethyl-I0-[4-( I -piperidino)-I -piperidino]carbonyloxy camptothecin, is a newly developed water-soluble camptothecin derivative now undergoing phase4 evaluation. In an attempt to establish whether the combination of CPT-I I with other standard anti-cancer agents would be of any benefit, we studied the effects of CPT-I I in combination with I I other anti-cancer agents on a human T-cell leukemia cell line, MOLT-3, in culture. We used both CPT-I I and SN-38 (active substance of CPT-I I in vivo), for our study. Cells were incubated for 3 days in the presence of 2 drugs (CPT-I I or SN-38 and another drug) and cytotoxic effects were determined by MlT assay. The effects of drug combinations on ID, were analyzed by an improved isobologram method. Supra-additive and marginal supra-additive effects (synergism) were observed for CPT-I I in combination with cisplatin, cytosine arabinoside and mitomycin C. Additive effects were observed for its combination with amsacrine, bleomycin, doxorubicin, etoposide, 5-fluorouracil, mitoxantrone and vincristine. Alternate sub-additive and protective effects (antagonism) were observed for CPT-I I in combination with methotrexate. Similar tendencies were observed for SN-38 in combination with other agents. These results suggest that CPT-I I in simultaneous administration with a majority of anti-cancer agents has an advantage for cytokilling. Of these agents, cisplatin, cytosine arabinoside and mitomycin C are most suitable for simultaneous administration with CPT-I I.