The role of concurrent chemoradiotherapy (CRT) in patients with non-small-cell lung cancer (NSCLC) unsuitable for radical therapy but who require locoregional treatment has not been defined. The aims of this phase I trial were thus to develop a novel regimen of weekly chemotherapy concurrent with high-dose palliative RT (40 Gy/20 fractions) and assess its tolerability, objective and symptomatic response rates. Eligible patients had stage I-IIIB NSCLC unsuitable for radical RT or limited stage IV disease, ECOG PS<or=1 and required locoregional therapy. Treatment was RT (40 Gy/20 fractions/5 per week) and weekly Vinorelbine plus Cisplatin escalated in six planned dose levels (DLs). At 4 weeks post-RT, patients received two cycles of Cisplatin 80 mg m-2 day 1+Vinorelbine 25 mg m-2 days 1, 8, 15. Dose-limiting toxicities (DLTs) were defined in the CRT phase. Disease-related symptoms were assessed by the Lung Cancer Symptom Scale. In all, 24 patients accrued, stage IIIB (n=12) and IV disease (n=10). The highest administered dose was at DL 4, Vinorelbine 30 mg m-2+Cisplatin 20 mg m-2 with DLTs of grade 4 neutropenia in two of three patients. No grade 3 or 4 nonhaematological toxicities were observed. The overall radiological response rate was 65% (n=23: complete response 4% and partial response 61%) and infield FDG-PET responses were seen in 89% (n=18). There was an improvement or stabilisation of symptoms and quality of life. Dose level 3, Vinorelbine 25 mg m-2+Cisplatin 20 mg m-2, is recommended for further assessment. This regimen was tolerable and produced meaningful responses for patients for whom locoregional control is required, but who are unsuitable for radical CRT.