Combined effect of bleomycin (BLM) and N-solanyl-N, N'-bis (3, 4-di-methoxy-benzyl)-ethylenediamine (SDB-ethylenediamine), a synthetic isoprenoid was studied on 3 oral squamous carcinoma cell lines (SCCTF, SCCKN, SCCRY) and clonal cell lines from SCCRY in vitro and on transplantable nude mouse tumors. The cytotoxicity of SDB-ethylenediamine varied among those cell lines in vitro. SDB-ethylenediamine potentiated more than 2-fold the cytotoxic effect of BLM in 6 cell lines, but no distinct correlation was found between cytotoxicity of SDB-ethylenediamine and potentiation by BLM. Compared with verapamil, the cytotoxic effect of BLM was potentiated 3.9-fold by SDB-ethylenediamine in SCCTF. The growth of the transplantable nude mouse tumors (SCCRY and SCCTF) was strongly suppressed when BLM was combined with SDB-ethylenediamine. Correlation between BLM resistance and potentiation of BLM by SDB-ethylenediamine was not observed in this experiment.