The pharmacokinetics of fluorouracil were examined after single 250-mg iv doses and 500-mg oral doses to female patients with breast cancer. In five patients who received intravenous fluorouracil, the mean peak plasma level of unchanged drug was 13.4 microgram/ml, the elimination half-life was 6.3 min, and the plasma clearance was 1410 ml/min. The last value is similar to the hepatic blood flow. In six patients who received oral fluorouracil, the mean peak value of unchanged drug in plasma, which occurred within 20 min of dosing, was 8.3 microgram/ml, and the fluorouracil elimination half-life was 7.2 min. The overall bioavailability of oral fluorouracil as unchanged drug was 28%, and the variation in plasma drug levels between individuals was similar following oral and intravenous doses. The data provide additional evidence of saturable hepatic metabolism of fluorouracil during the first pass.