OBJECTIVE This study was designed to evaluate the feasibility and efficacy of accelerated hyperfractionated thoracic radiotherapy concurrently combined with daily carboplatin in patients with locally advanced, unresectable nonsmall cell lung cancer. METHODS Thirty-one patients with locally advanced nonsmall cell lung cancer were treated with continuous course, twice daily thoracic radiotherapy (1.5 Gy each) to a total of 60 Gy over 4 weeks. Carboplatin (25 mg/m2) i.v. was given immediately before each morning thoracic radiotherapy. Blood samples were taken to measure the blood free platinum pharmacokinetics on day 1. RESULTS All 31 patients completed the protocol treatment without delay. The median age was 73 years, and the majority had Stage IIIA (32%) or IIIB (48%) disease. Major acute toxicity (> or = Grade 3) included 17 patients (55%) with leukopenia, 5 patients (16%) with thrombocytopenia, and 7 patients (23%) with esophagitis. One possible treatment-related death due to diffuse pneumonitis was observed. There were three complete responses (CRs) and 23 partial responses (PRs) in the radiation field, for a response rate of 84%. The relapse pattern was predominantly loco-regional, and the median survival time was 9.8 months. The area under the plasma level-time curve (AUC) of free platinum correlated significantly (r = -0.41, p = 0.04) with the surviving fraction of leukocytes, but not with the severity of the esophagitis. Responders had significantly (p = 0.04 by Welch's t-test) higher AUCs than nonresponders. CONCLUSIONS This combination therapy was feasible and efficacious against locally advanced nonsmall cell lung cancer. Although long-term local control still remains unsatisfactory, pharmacokinetic data are suggestive of a role for platinum in enhancing the radiation effect.