Eniluracil (776C85, GW776) inactivates dihydropyrimidine dehydrogenase (DPD), the principal enzyme of 5-fluorouracil (5-FU) catabolism. Inactivation of DPD eliminates a potential mechanism for tumor 5-FU resistance and permits achievement of reliable and predictable pharmacokinetics following oral 5-FU administration. Eniluracil/5-FU has demonstrated efficacy as monotherapy in patients with a variety of solid tumors when given on a 5 or 28-day dosing schedule. The primary and dose-limiting toxicity is myelosuppression with the 5-day schedule and diarrhea with the 28-day schedule. The frequency of hand-foot syndrome is minimal with either schedule. Phase III pivotal registration-directed studies with eniluracil/5-FU given by the 28-day schedule are ongoing or planned for the near future in patients with advanced colorectal, breast and pancreatic cancer.