The serum of lactating rats that have never been infected with the protozoan parasite Trypanosoma lewisi contains a rheumatoid factor-like immunoglobulin M (IgM). This IgM amplifies a specific immunoglobulin G (IgG) response to the parasite and accounts for the unusual resistance of previously uninfected lactating rats and their suckling pups to infection with T. lewisi. A similar rheumatoid factor-like IgM, which is induced late in the usual course of infection with T. lewisi in nonlactating rats, amplifies an earlier IgM response and terminates the infection. To our knowledge, this is the first description of a rheumatoid factor, which is classified as an autoimmune antibody, acting in a protective manner.

DL-ct-Difluoromethylornithine, a polyamine biosynthesis inhibitor, and bleomycin, a currently used antineoplastic agent, have each previously been shown to be curative for acute short-term infections of mice with Trypanosoma brucei brucei, an African trypanosome closely related to those that cause the human disease African sleeping sickness. These agents were tested singly and in combination in a previously described mouse model of sleeping sickness with demonstrable brain involvement. The original model is extended by using two additional strains of outbred mice and by demonstrating that melarsoprol, an arsenical and currently the only drug used for human African trypanosomiasis involving the brain, was also curative for these brain infections. Neither difluoromethylornithine nor bleomycin alone was curative for the brain infections; however, many combinations of the two drugs were found to be 100% curative with no evidence of immediate toxicity.Human African trypanosomiasis, or sleeping sickness, is caused by either of two subspecies of Trypanosoma brucei, T. brucei gambiense and T. brucei rhodesiense. Although this tsetse flytransmitted disease has been controlled in many parts of Africa, outbreaks continue to occur. A recent example is the epidemic occurring in Uganda (1). Drugs available to treat this disease are generally quite toxic and not always curative; no new drugs have been introduced in the last 30 years. Melarsoprol, a toxic organic arsenical, is the only available drug that is effective in patients with advanced sleeping sickness-i.e., with central nervous system (CNS) involvement (2, 3).A major obstacle in the development of new drugs over the years has been the lack of a convenient and reliable laboratory model of the CNS infection. Recent studies of Jennings and colleagues (4)(5)(6) have demonstrated that a strain (TREU 667) of T. brucei brucei, a veterinary parasite, establishes CNS infections in mice and may thus provide a model of CNS trypanosomiasis. These semichronic infections are resistant to Berenil (diminazene aceturate), a widely used veterinary drug, if treatment is delayed for 3 weeks, even though such treatment ini-

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