Fifty-seven patients were treated with continuous infusion of PALA at a dose of 850 mg/m2/day x 5 and iv bolus injection of 5-FU at a dose of 300 mg/m2/day x 5, which was given at the end of each 24-hour PALA infusion; the treatment interval was 28 days. The overall response rate among 43 evaluable patients was 14%. Two of 21 patients (10%) with colorectal carcinoma, two of eight patients with pancreatic carcinoma, and two of four patients with breast carcinoma achieved partial responses lasting 2-12 months. One of the responding patients with colon cancer and two with breast cancer had failed to respond to prior therapy with 5-FU; one of the responding patients with breast cancer had previously received an inadequate trial of a similar regimen. Toxic effects were mild to moderate and were confined to oral mucositis in most patients. It is concluded that this regimen offers little enhancement of the antitumor activity of 5-FU in patients with colorectal cancer previously treated with 5-FU. Investigation of other infusion techniques for the PALA and 5-FU combination is recommended, with particular attention to the treatment of colorectal, pancreatic, and breast carcinomas.