The results are reported of three chemotherapy schedules in a multicentric, international, randomized trial of the therapy of unresectable non small cell lung carcinoma which included 612 patients. The antitumoral efficiency of the cisplatin + vindesine combination (200 patients) was compared with that of navelbine (206 patients), a recently available vinca alkaloid, and with a third therapeutical leg with cisplatin + navelbine (206 patients). After a very thorough response evaluation the combination cisplatin + navelbine obtained a response rate higher than the other combination (30% vs. 19%; p = 0.02) and also than navelbine (30% vs. 14%; p < 0.001). The median response durations were 9.3, 9.9, and 7.8 months for the combination with navelbine, vindesine and the new vinca alkaloid alone, respectively. After a median follow-up period of 26 months the combination cisplatin + navelbine achieved a higher survival rate than the combination cisplatin + vindesine (40 vs. 32 weeks) and navelbine (40 vs 31 weeks; p = 0.045). The most important toxicity with the combination cisplatin + navelbine was neutropenia, which although relevant in number was not of long duration. In summary, navelbine is an active agent in the therapy of non small cell lung carcinoma. In this trial the therapeutic superiority of its combination with cisplatin over the combination cisplatin + vindesine was observed; likewise, it was also more efficient than monotherapy with navelbine.