Background: Many regimens of gemcitabine–cisplatin chemotherapy have proven activity in patients with advanced non-small cell lung cancer (NSCLC). However, the optimal dose and schedule still have to be established. Patients and methods: We conducted a phase II study with administration of cisplatin 50 mg/m 2 on days 1 and 8 and gemcitabine 800 mg/m 2 on days 2, 9 and 15. This schedule was selected to optimise the synergism between the two drugs and reduce toxicity due to high dose cisplatin. Results: Thirty-six chemo-naive patients with stage IIIA, IIIB or IV NSCLC entered the study (26 men, 10 women; median age 58 years, range 29–74). Twenty patients achieved a partial response: 7 out of 10 stage IIIA patients, 7 out of 13 stage IIIB patients and 6 out of 13 stage IV patients. On intent-to-treat basis, the overall response rate (RR) was 58% (95% confidence interval, 42–74%). Ninety percent of stage IIIA patients and 46% of stage IIIB patients received adjuvant surgery or radiotherapy. Overall median duration of response was 28 weeks (range 6–147 weeks). For stage IIIA, IIIB and IV patients, these numbers were 91, 13 and 23 weeks, respectively. One-year survival was 49% with 90%, 23% and 42% for stage IIIA, IIIB and IV patients, respectively. The main toxicity was myelosuppression. WHO grades 3 and 4 leukopenia occurred in 67% of patients, whereas 61% experienced grade 3 or 4 thrombocytopenia. Although hematological toxicity was clinically tolerable, it frequently led to omission of gemcitabine administration on day 15. The incidence of non-hematological toxicity was very low. Conclusion: This regimen of cisplatin on days 1 and 8 and gemcitabine on days 2, 9 and 15 induced a high RR in patients with advanced NCSLC. Frequent omission of gemcitabine day 15 is a limitation of this schedule. This should be an important factor in a practical approach to decide on the most optimal schedule of the cisplatin plus gemcitabine combination.