The optimal chemoradiation regimen for stage III non-small cell lung cancer (NSCLC) has not been determined. In this phase I/II study, the use of twice-weekly paclitaxel concomitant with weekly cisplatin and thoracic radiotherapy (RT) was evaluated. Patients with stage III NSCLC (without pleural effusion or cervical lymphadenopathy) were treated with thoracic RT (60 Gy in 30 fractions over 6 weeks) with concurrent weekly cisplatin 20 mg/m(2) and escalating doses of twice-weekly paclitaxel (starting dose of paclitaxel of 20 mg/m(2) increased in increments of 5 mg/m(2)) in successive cohorts of three to six patients until two or more patients experienced dose limiting toxicities (DLTs) at a particular dose level. All patients were planned to be given a further two cycles of consolidation chemotherapy consisting of paclitaxel 175 mg/m(2) and carboplatin AUC 5 after completion of RT. Twenty-five patients were enrolled in this study from two institutions. At a dose of paclitaxel 35 mg/m(2), two of four treated patients had DLTs (1 grade 3 oesophagitis and pulmonary toxicity; 1 grade 3 oesophagitis and infection). The recommended dose was therefore determined to be 30 mg/m(2) and a total of 15 patients were enrolled in an expanded cohort at this level. The overall response rate for all patients was 64% (95% CI: 43-82%). The estimated median survival was 23.6 months with an estimated 1-year and 2-year survival of 72 and 49%, respectively. Paclitaxel can be safely given twice-weekly at a dose of 30 mg/m(2) in combination with weekly cisplatin (20 mg/m(2)) and thoracic RT (60 Gy), and this regimen has significant activity in stage III NSCLC.