Mice infected with Leishmania donovani were maintained on various purified diets. The infection in the normal mouse was characterized by a rise in parasite numbers over 1 to 4 weeks, followed by a number crisis which led to a low grade chronic infection of indefinite duration. A study of the influence of vitamin and protein deficiencies on this course of infection was undertaken. The administration of desoxypyridoxine (a pyridoxine analogue) to mice fed either basic or pyridoxine-free rations prior to infection resulted in an increase in the rate of accumulation of parasites observable as early as eight days after infection. The daily administration of pyridoxine to these deficient mice was found to reverse this effect. Pyridoxine deficiency induced later in the course of infection also resulted in increased parasite densities, and, in addition, did not allow the normal decrease in parasite numbers, after peak day, to occur. Pantothenic acid-deficiency was shown to have a dual effect on the number of L. donovani in the mouse. The injection of pantoyl taurine (a pantothenic acid analogue) and/or the deletion of pantothenic acid from the diet of the mouse resulted in a suppression of parasite numbers over the first 15 days of infection. After this time, an increase in the rate of accumulation of parasites was observed in pantothenate-deficient mice. Under the conditions of these experiments, the course of leishmaniasis was not altered in mice made thiamine deficient prior to or subsequent to infection. Mice placed on a protein-free diet prior to or following infection harbored significantly higher parasite burdens than those of pair-fed or ad libitum controls. The increase in parasite numbers resulting from protein depletion was found largely to be reversed by placing the deficient animals on an adequate diet.