Effects of Oral administrations of uridine were investigated in a study of six healthy volunteer control subjects and nine patients with metastatic colorectal cancer. Oral uridine was studied as single-dose administrations at dosesescalating from 0.3 to 12 g/m2 and as multiple-dose administrations every 6 hours for 3 days at doses from 5 to 10 g/m2. The maximum tolerated dose (MTD) was 10 to 12 g/m2 for a single dose of uridine and 5 g/m2 for the multiple-dose regimen. Diarrhea was the dose-limiting toxic effect. Single-dose oral uridine resulted in an increase in plasma uridine concentrations in the range of 60 to 80 μM after doses of 8 to 12 g/m2. At these doses, Bioavailability of oral uridine ranged from 5.8% to 9.9%. At the MTD of 5 g/m2 in the multiple-dose uridine schedule, steady-state plasma uridine levels of approximately 50μ were achieved. Further Studies should explore the role of oral uridine in the modulation of the toxicity of fluorouracil. [J Natl Cancer Inst 83:437–441, 1991]