Reversal of methotrexate toxicity in mice by 5-methyltetrahydrofolic acid

1. Mice have been compeletly protected against the lethal effects of repeated injections of methotrexate by 5-methyltetrahydrofolic acid. Methotrexate-resistant cells probably owe their resistance to their high content of this substance.2. Daily small doses were much more effective than fewer but larger doses.3. The reduced efficiency found in counteracting high dosages of methotrexate may be due to interference with folate transport across cell walls.4. 5-Methyltetrahydrofolic acid and citrovorum factor did not differ greatly in their ability to inhibit methotre toxicity. It is suggested that the pharmaceutical effects of citrovorum factor are due to its conversion to 5-methyltetrahydrofolic acid.