The purpose of this study was the determination of the maximum tolerable dose (MTD) of weekly paclitaxel (PX) in combination with 3D-conformal radiotherapy in non-small cell lung cancer (NSCLC) and the evaluation of side effects, patient outcome and tumor response. Thirty-eight patients with inoperable NSCLC, UICC-stage IIIA (n=14)/IIIB (n=24) received two cycles of induction chemotherapy with PX/carboplatin followed by combined radiochemotherapy (60 Gy/6 weeks) with weekly PX which was escalated in cohorts of four patients until dose limiting toxicity (DLT) was reached. Starting level was 40 mg/m(2). 3D-conformal radiotherapy was applied in all patients. Toxicity was determined by WHO criteria. Patients were followed-up 3-monthly. Thirty eight patients have entered the study, 34 patients are evaluable. DLT was esophagitis III degrees, requiring interruption of radiotherapy and was reached at the PX 70 mg/m(2). Two hypersensitivity reactions (50 mg/m(2)) and one leucopenia III degrees (60 mg/m(2)) were observed. Only one patient (60 mg/m(2), 50 Gy) completely aborted treatment. The pneumonitis rate was between 21 and 36% but showed no clear correlation with PX dose. Tumor response (PR and CR) defined by CT-scan 6 weeks following radiotherapy was 88% (30/34). The 1- and 2-year survival rate is 73% and 34%. We conclude that the MTD of weekly PX with 60 Gy normofractionated radiotherapy is 60 mg/m(2). The DLT is esophagitis. Response and survival data of this sequential/combined approach are promising. A minor increase of pulmonary toxicity of irradiation is suspected.