A metabolic imbalance technique was employed to study vitamin B(12) deficiency in rats infected with Trypanosoma lewisi. Throughout the observational period, animals on the deficient diet had lowered serum vitamin B(12) levels compared with complete and pair-fed animals. The decline in the level of the vitamin, ten days after the initiation of the experiment, continued progressively until the termination of the study. Body weight gains and food consumption in rats on complete, vitamin B(12)-deficient, or pair-fed diets and inoculated with T lewisi showed significant increase over inoculated controls. The rates of body weight and food consumption in vitamin B(12)-deficient animals were significantly less than that of the adequately fed animals.The indices of lowered resistance to infection in the vitamin B(12)-deficient rats were manifoid. Deficient rats suffered earlier and higher parasitemia followed by persistent infection. The delay in the synthesis of the reproductive inhibiting antibody (ablastin) resulted in prolonged variability in the length of the trypomastigotes. Severe depression in the primary and secondary antibody responses (IgG and IgM) to in vivo immunization of sheep erythrocytes was also observed in the deficient animals. In comparison, the level of IgG antibody decreased approximately one fifth the control values.