AbstractMucositis is one of the major problems encountered after the administration of systemic chemotherapy. Leucovorin, routinely used as a rescue agent for methotrexate may reduce toxicity, but may also reduce the effectiveness of the chemotherapeutic agent. If leucovorin is administered as a mouth wash, local toxicity may be reduced without loss of methotrexate efficacy. In order to study this, 15 normal human volunteers were given leucovorin mouth wash and then had plasma determinations of 5-methyl-tetrahydrofolate and citrovorum factor. Small but statistically significant increases in plasma levels of 5-methyl-tetrahydrofolate were observed with no increase in levels of plasma citrovorum factor. It is concluded therefore that a small amount of leucovorin is absorbed systemically when administered as a mouth wash, but such an amount would most likely not be significant enough to reduce the effect of methotrexate therapy, but may reduce mucositis.