Chromosome translocations involving 11q23 are associated with a number of different types of leukemia. These translocations fuse a gene encoding a putative transcription factor, HTRXI, to genes on other chromosomes. We report cloning and sequencing the t(X;11) breakpoint region from a cell line established from an infant with acute lymphocytic leukemia. The gene AFXI, on the X chromosome, is expressed in a variety of cell types. Sequence analysis indicates a high degree of homology between AFXI and the forkhead family of transcription factors. The high degree of identity within the forkhead region and the lack of homology outside that region suggest that AFXI represents a novel forkhead family member. It is predicted that a chimeric fusion protein with altered DNA binding activity will be the result of the translocation.