Trypanosome infections in man and animals result in marked suppression of immune responses. The immune response of inbred mice, infected with strains of T. brucei which produce acute, subacute, or chronic disease, will be analyzed as completely as possible. In vivo observations will be made on the course of the infection and on humoral and cell-mediated responses to the trypanosomes, in normal and in nude (athymic) mice, as well as in mice treated with agents (x-ray, drugs, ALS, adult thymectomy) which affect known subpopulations of lymphocytes. Specific in vitro responses (lymphocyte transformation, lymphokine production, cytotoxicity) will be followed in parallel, using both crude trypanosome sonicates and partially purified fractions as antigens. Responses to other antigens (SRBC, thymus-independent polysaccharide antigens, oxazolone) will also be examined in the infected animals and in cultures of their lymphoid tissues, as well as proliferative and other responses to nonspecific stimuli (mitogens). Passive (humoral) and adoptive (cellular) transfer of immunity and/or suppression of specific and nonspecific responses will be attempted in vivo and in vitro, using known immunoglobulins, whole lymphocyte populations, or subpopulations characterized or purified with respect to standard lymphocyte markers (Thy-1; Ly-1,2, and 3; glass or nylon wool adherence; Fc and C3 receptors, etc.). Particular effort will be directed to in vitro study of cell contact effects leading to inhibition of responses and to possible production of "immunoregulatory" lymphokines (LK) which inhibit antibody formation and release, lymphocyte transformation, or other parameters of cell-mediated immunity. Evidence for the release of such LK will be sought in infected animals. Finally the effect will be explored of nonspecific agents (x-ray, drugs, etc.) and of specific immunization with whole organisms or their fractions, given by various routes and schedules, in altering the balance in vivo among immune, helper, and suppressor effects.