In the treatment of neoplastic diseases, the therapeutic use of folate antagonists such as methotrexate is often accompanied by the concurrent or subsequent administration of 5-formyltetrahydrofolate (folinic acid, leucovorin) in order to reverse its effects (Mead et al., 1963; Hryniuk and Bertino, 1969). In vitro, this reduced folate is readily altered by acid conditions (May et al., 1951) such as may exist in the stomach, and it has, therefore, been administered parenterally. It has been recognized for some time (Nixon and Bertino, 1972) that an effective, orally administered, reduced folate would have a useful place in the increasing use of cancer chemotherapy, and effective absorption of oral doses up to 1 mg has been demonstrated (Chanarin, 1969; Nixon and Bertino, 1972). Such doses are small compared to those employed therapeutically (often greater than 20 mg) and further evidence of acceptable absorption in this dose range would be desirable. Each of three pairs of healthy Caucasian male volunteers (Table) were ran-