The use of leucovorin orally in normal and leukemic L1210 mice to prevent the toxicity and gastrointestinal lesions caused by high doses of methotrexate.

Leucovorin p.o. was as effective as parenterally in pre venting weight loss and toxic deaths in normal mice from high doses of methotrexate. Histological sections of proxi mal jejunum demonstrate the protection afforded by de layed p.o. leucovorin from the marked disruption of villi and mucosal glands produced by methotrexate. Mice bearing leukemia L1210 treated with methotrexate plus leucovorin p.o. were able to tolerate 2to 4-fold increases in the dose of methotrexate tolerated by mice treated with methotrexate alone. This resulted in a greater in crease in survival time of leukemic mice. The therapeutic advantage of the regimen of delayed leucovorin given in conjunction with methotrexate is maintained when leu covorin is administered p.o.