Taxanes have clearly demonstrated activities against gastric cancer. We compared the combination of paclitaxel plus 5-fluorouracil (5-FU) (PF) with docetaxel plus 5-FU (DF) as first-line chemotherapy in patients with measurable metastatic gastric cancer. Seventy-seven patients were randomly assigned to receive paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 on day 1, in combination with 5-FU 500 mg/m2 continuous infusion on days 1-5. Treatment was repeated every 3 weeks. Of 314 chemotherapy cycles delivered (median 5 in both groups), dose reduction was required more frequently in the DF group, being 9 and 19%, respectively (P<0.01). PF was associated with, although statistically insignificant, substantially less grade 3 or 4 toxicities than DF (68 versus 85%; P=0.09). Global quality of life was similar in both groups, but substantive differences in many symptom scores including pain, dyspnea, constipation and diarrhea favored PF. There were no significant differences in therapeutic efficacy between PF and DF with respect to response rate (42 versus 33%, respectively; P=0.53), and failure-free (3.6 versus 4.2 months; P=0.92) and overall survival (9.9 versus 9.3 months; P=0.42). Both PF and DF appear to have efficacy against metastatic gastric cancer, with different, but acceptable, safety profiles.