To study the genetic parameters of resistance to Trypanosoma congolense infection, highly susceptible BALB/c and relatively resistant C57BL/6 mice were crossed to produce reciprocal F1 and F2 offspring. Mice were infected with T. congolense and monitored for parasitemia within the first 2 wk and also for their survival periods. BALB/c mice showed unrestrained parasite growth to the time of death (median survival period, msp = 12.0 days), whereas in C57BL/6 mice, parasitemia reached an initial peak on day 6 and was followed by a rapid apparent clearance of the parasites in an average period of 3 days. Their msp was 163.0 days. The F1 mice cleared the parasites, following the first peak of parasitemia, in an average period of 4 days and had an msp of 69.5 days. Thus, the F1 offspring displayed an intermediate phenotype between susceptible and resistant parents in terms of parasite clearance and survival period. Resistance in F2 mice, as measured by survival times, was inherited as a polygenic trait. Among F2 mice, there was an inverse correlation between the time taken to clear the initial wave of parasitemia and the survival period, r = -0.58; P < 0.05. Thus, the pattern of control of the parasites following the first peak of parasitemia appears to be a good predictive factor for the survival period of mice infected with T. congolense.