Purpose: The combination of Gemcitabine (GEM)/carboplatin (CBDCA) has demonstrated activity in the treatment of stage III and IV non-small-cell lung cancer (NSCLC). This phase III randomized trial compared the response rate, survival rate, and toxicity of the combination of GEM plus CBDCA with the combination of VLB plus CDDP., Methods: Chemonaïve patients with advanced or metastatic NSCLC were enrolled in the study. Pts were randomized by coin method to receive either cisplatin (CDDP) 70 mg/m(2) on day 1 plus vinblastine (VLB) 6 mg/m(2) on days 1 and 8 (arm A) or gemcitabine 1000 mg/m(2) on days 1 and 8 plus carboplatin 300 mg/m(2) on day 1 (arm B). Both regimens were administered on a 21-day course., Results: A total of 198 patients (99 pts each in arms A and B) were enrolled in the study between July 1997 and April 2000. All pts had an ECOG performance status < or=2. Patients had a median age of 58 years (range, 49-67) in arm A and 59 years (range, 49-69) in arm B. In arm A, there were 15 partial responders (PR), for an overall response rate (ORR) of 15%, compared with three complete responders (CR) and 24 PR, for an ORR of 27% (P<0.05), in arm B. Mean survival times were 7.9 months (95% CI, 7.1-8.0) in arm A and 11.6 months (95% CI, 10.0-13.0) in arm B. One-year survival rates for arms A and B, respectively, were 13 and 36%. Numbers of pts with WHO grad 3/4 hematologic and non-hematologic toxicity in arms A/B were leukopenia 0/2, thrombocytopenia 0/2, alopecia 46/33, neurotoxicity 2/1, and asthenia 35/42., Conclusion: The GEM/CBDCA combination showed a higher therapeutic response, an improved 1-year survival, and a similar toxicity profile compared with the VLB/CDDP combination.