PURPOSE: To evaluate the radiation enhancement by a combination of CPT-11 and etoposide, with in vitro ionizing radiation. MATERIALS AND METHODS: H460 human lung carcinoma cells were plated, and treated with 4.5 microM CPT-11 for 4 hr, then irradiated with various doses of radiation, and treated with 1microM etoposide for 1.5 hr. The survival and sublethal damage recovery (SLDR) were determined by a clonogenic assay. The analysis of apoptosis, due to the combined treatment with drugs and radiation, was performed using 7-AAD staining and flow cytometry. RESULTS: The survival experiments resulted in radiation dose enhancement ratios (DER) of 1.30, 1.39, and 1.65 for CPT-11, etoposide, and CPT-11 plus etoposide, respectively. The analysis of apoptosis, using 7-AAD staining and flow cytometry, indicated an synergistic effect. Inhibition of the SLDR was not observed with the CPT-11 plus etoposide. CONCLUSION: These data show that the combination of CPT-11 and etoposide is a more effective radiation enhancer in human lung cancer cells than either agent used individually in human lung cancer cells. This radiation enhancement is not caused by the inhibition of the SLDR, but other mechanisms may be involved in the combined treatment of CPT-11 and etoposide combined treatment.