It has been suggested that combination high dose rate (HDR) intraluminal brachytherapy and photodynamic therapy (PDT) in nonsmall cell lung cancer (NSCLC) may improve efficacy of treatment, reduce toxicity and enhance quality of life for patients. To provide a cellular basis for this we examined the in vitro sensitivity of MRC5 normal lung fibroblasts and four NSCLC cell lines following HDR radiation, PDT and combined HDR radiation and PDT. HDR radiation was cobalt-60 gamma rays (1.5-1.9 Gy min(-1)). For PDT treatment, cells were exposed to 2.5 microg mL(-1) Photofrin for 18-24 h followed by light exposure (20 mW cm(-2)). For combined treatment cells were exposed to Photofrin and then either exposed to light and 15-30 min later exposed to HDR radiation or exposed to HDR radiation and 15-30 min later exposed to light. D(37) values calculated from clonogenic survival curves indicated a six-fold difference in HDR radiation sensitivity and an eight-fold difference in PDT sensitivity. The effect of combined treatment was not significantly different from an additive effect of the individual treatment modalities for the NSCLC cells, but was significantly less than additive for the MRC5 cells. These results suggest an equivalent tumor cell kill may be possible at reduced systemic effects to patients.