An uncomplicated deficiency of folic acid has been produced by dietary means in young mice of various strains in three to six weeks without the aid of a folic acid antagonist or a sulfa drug. This has been done by keeping mice in cages with screen bottoms (to prevent coprophagy) and feeding them a synthetic diet low in folic acid containing 20 per cent casein, 8 per cent gelatin, and 0.8 per cent methionine, in addition to the other usual ingredients. The deficiency may be overcome by feeding 0.5 mg or more pteroylglutamic acid per kg of diet or by feeding larger amounts of para-aminobenzoic acid or procaine penicillin G. The folic acid deficient mice have been used to study the relationship of nutrition of infection with the virus of lymphocytic choriomeningitis and to certain transplantable lymphocytic neoplasms. With both types of infection the time of death was significantly delayed in folic acid deficient mice. These studies provide a new tool which may be used to study the relationships between folic acid and disease in normal intact mice not receiving drugs.