Effectiveness of chemotherapy has been demonstrated in stage IV non small cell lung cancer as well as in stage IIIb disease when combined with radiotherapy. A significant improvement of both survival and quality of life was shown and is thought to be associated with higher efficiency. Therefore, treatment of relapses is now a question of practical interest. Ninety-seven non small cell lung cancer patients who were delivered a second line chemotherapy following primary chemotherapy alone were reviewed. Sixty-five patients were administered a 2 drug cisplatin-based regimen (with etoposide, bleomycin or vinorelbine). Twenty eight patients received no cisplatin but the cyclophosphamide, epirubicin combination or any 2-drug regimen assembled from the following agents: etoposide, mitomycin, ifosfamide. The last 4 patients were given single-agent vinorelbine. Fifteen objective responses (15.2%) (95% CI: 9-24%) were observed. The median response duration was 27 weeks. Response rates were 18.4% (95% CI 9-28%) and 9.3% (95% CI: 0-19%) in cisplatin-based combinations and in other regimens, respectively. No difference in response rates was observed between primary responsive and non responsive patients but response rates were influenced by the choice of the first line combination chemotherapy.