Complete protection against a monomorphic strain of Trypanosoma gambiense has been obtained by the passive transfer of antibody to infected mice and rabbits. The necessary experimental conditions for protection appear to be: (1) a sufficiently high protective antibody titer; and (2) the injection of a sufficiently small challenge inoculum. Evidence is presented which is consistent with the hypothesis that relapses in experimental infections are due to the selection of an antigenic mutant from a heterogeneous population. It is therefore assumed that a small challenge injection is necessary to decrease the probability of the presence of an antigenic mutant in the challenge inoculum. In our system, each trypanosome is not capable of changing its antigenic composition. Complete protection of warm-blooded vertebrates against African trypanosomes has occasionally been reported [reviews by Taliaferro (1929) and Soltys (1963)]. In general, however, challenged animals immunized with crude blood trypanosome homogenates, soluble blood trypanosome antigens [exoantigens, PR antigen (s)], or passively treated with antibody, show only increased survival times (Inoki et al., 1951; Weitz, 1960; Seed, 1963; Miller, 1965; Seed and Gam, 1966). In our studies on complete protection, several assumptions were made. (1) Relapses may be due to the selection of an antigenic mutant from a heterogeneous population by either host antibody or passively transferred antibody from a donor animal. Strong evidence in favor of this hypothesis has been obtained by Watkins (1964) with Trypanosoma brucei. This is in contrast with the views of Inoki et al. (1956) who suggested that antibody induces antigenic changes in each individual Trypanosoma gambiense. (2) The rate of spontaneous antigenic mutation in T. gambiense is not abnormally high. We have assumed a priori the rate to be less than 1/106 cells. The rate of spontaneous antigenic mutation in T. brucei has been shown to be less than 1/105 trypanosomes (Watkins, 1964). (3) If sufficient antibody to T. gambiense is present complete protection can be obtained experimentally. It is also necessary to inject (challenge) animals with a sufficiently small number of trypanosomes to avoid the statistical possibility of there being Received for publication 22 June 1966. * This work was supported by a research contract (DA contract 49-193-MD-2817) from the U. S. Army Medical Research and Development Command, Office of the Surgeon General. an antigenic mutant present in the inoculum. This paper presents evidence to show (A) that complete protection can consistently be obtained, and (B) that relapses in T. gambiense may also be due to selection of antigenic mutants from the population. METHODS OF PROCEDURE Strains of trypanosomes Six strains (TS, TS-1, TS-2, TS-3, TS-4, and TS-5) of the blood form of Trypanosoma gambiense were used in these experiments. The TS strain of T. gambiense and its relationship to strain (TS-1) and (TS-2) was described by Seed, Baquero, and Duda (1965) and Seed and Gam (1966). Figure 1 shows the relationships between (TS-2), (TS-3), (TS-4), and (TS-5). These strains were maintained by syringe passage every 2nd day through 20-g white mice. The method used to harvest the blood trypanosomes was described by Seed and Baquero (1965). Five-kilogram rabbits were infected by inoculating them intraperitoneally with varied doses of trypanosomes in infected mouse blood, or with washed suspensions of trypanosomes free of any mouse blood eleme ts. Rabbits were bled 14 to 18 days following infection. Rabbits, at this time, have previously been shown to contain maximum protective antibody titers to the original infecting strain (Seed and Gam, 1966). Isolation of trypanosomes Mice were bled at peak parasitemia by heart puncture. One per cent sodium citrate (w/v) was used as the anticoagulant. The suspension was centrifuged at 500 g in an International Clinical Centrifuge for 4 min. After centrifugation the serum and trypanosome layers were removed from the underlying red cell layer with a Pasteur pipette. The serum and trypanosome suspension was then centrifuged at 1,000 g for 4 min in a clinical centrifuge, and the serum layer removed. The trypanosomes were resuspended in Ringer's phosphate (0.1M NaCl, 0.06M KCl, 0.02M MgSO4, and 0.025M ph sphate buffer, pH 7.2) containing (0.01M) glucose and recentrifuged for 4 min at 1,200 g. The