• Minimizes hematologic effects of high-dose methotrexate therapy (leucovorin rescue).

• Advanced colorectal carcinoma (with 5-fluorouracil).

• Management of overdoses/prevention of toxicity from folic acid antagonists (pyrimethamine, trimethoprim, trimetrexate).

• Folic acid deficiency (megaloblastic anemia) unresponsive to oral replacement.