Chemotherapy for cervical cancer patients with recurrent and/or advanced disease has been complicated by excessive toxicity and short duration of responses, leading to little or no improvement in survival. Modification of drug scheduling and delivery of platinum, bleomycin, methotrexate, and 5-FU has resulted in a new combination regimen with little toxicity and a survival advantage for responders. PBM (platinum 80 mg/m2 D1, bleomycin 10 mu/m2/day D3-6, methotrexate 150 mg/m2 D15, 22 with leucovorin) is alternated with PFU (platinum 100 mg/m2 D1, 5-FU 1000 mg/m2/day D2-5) q 4 weeks for 3-6 months. The platinum, bleomycin, and 5-FU were delivered by continuous infusion. Twenty-three patients with recurrent and 17 with advanced cervical cancer are evaluable; 91% of patients with recurrent disease had received prior radiation therapy. The response rate was 30.4% in those with recurrent disease, and 41.2% in those with advanced disease, with 86 and 42.9% of responders respectively achieving a CR. Survival data were analyzed for each group separately, as well as for the combined recurrent/advanced disease group (N = 40). The results and significance were not changed by the groupings. In the combined recurrent/advanced group, median duration of response was 10.5 months, mean 20.1, and the median overall survival was 11 months, mean 20.5 +/- 3.5. There was a survival advantage accrued to the responders (median, 28 months) vs the nonresponders (10 months) (P = 0.0005 by log rank test). Moreover, there was a significant difference in progression-free interval between responders vs nonresponders (P = 0.0001), as well as between responders and those with stable disease (P = 0.001). This regimen was very well tolerated and there was no significant pulmonary toxicity. Furthermore, in the subset of 23 patients who had recurrent disease, 67% achieved palliation of pain. Experience with this protocol supports the continuing use of chemotherapy in the management of cervical cancer patients.