Trypanosomosis, or sleeping sickness, is a major disease constraint on livestockproductivity in sub-Saharan Africa. To identify quantitative trait loci (QTL)controlling resistance to trypanosomosis in cattle, an experimental cross wasmade between trypanotolerant African N'Dama (Bos taurus) and trypanosusceptibleimproved Kenya Boran (Bos indicus) cattle. Sixteen phenotypic traits weredefined describing anemia, body weight, and parasitemia. One hundredseventy-seven F2 animals and their parents and grandparents were genotyped at477 molecular marker loci covering all 29 cattle autosomes. Total genomecoverage was 82%. Putative QTL were mapped to 18 autosomes at a genomewise falsediscovery rate of <0.20. The results are consistent with a single QTL on 17chromosomes and two QTL on BTA16. Individual QTL effects ranged fromapproximately 6% to 20% of the phenotypic variance of the trait. Excludingchromosomes with ambiguous or nontrypanotolerance effects, the allele forresistance to trypanosomosis originated from the N'Dama parent at nine QTL andfrom the Kenya Boran at five QTL, and at four QTL there is evidence of anoverdominant mode of inheritance. These results suggest that selection fortrypanotolerance within an F2 cross between N'Dama and Boran cattle couldproduce a synthetic breed with higher trypanotolerance levels than currentlyexist in the parental breeds.