The copper-deficient rat-trypanosome system was used to study copper deficiency in Sprague Dawley rats infected with Trypanosoma lewisi. Throughout the observational period, animals on the deficient diet had lower plasma and liver copper concentrations compared with complete and pair-fed animals. In all dietary groups, the food intake and body weight changes of rats inoculated with T lewisi showed significant increases over the noninoculated controls. The rate of these indices were significantly less in the copper-deficient animals compared with the animals fed complete diets. Copper-deficient and pair-fed control rats showed greater numbers of parasites than controls throughout the infection. The duration of the trypanosomal infection was longer in copper-deficient rats compared with other groups. In all of the dietary groups, severe depression in the primary and secondary antibody responses (IgM and IgG) to in vivo immunization with sheep erythrocytes was observed in infected animals over noninfected controls. The results of the present study indicate that during copper deficiency, there are significant changes in food consumption and body weight and enhanced susceptibility to infection as measured by an increased parasitemia and depression in the antibody responses.