Breakpoints of the t(8;21) chromosome translocation in acute myeloid leukemia are clustered within the human gene, AML1, located on chromosome 21 [Miyoshi, H., Shimizu, K., Maseki, N., Kaneko, Y. & Ohki, M. (1991). Proc. Natl. Acad. Sci. USA, 88, 10431-10434]. The product of AML1 has a region about 130 amino acids long that is highly homologous to the Drosophila segmentation gene runt (runt homology region). The cDNA isolated from mouse fibroblasts encoding the alpha-subunit of polyomavirus enhancer binding protein 2 (PEBP2/PEA2) revealed that it also has a runt homology region (E. Ogawa et al., submitted). In this study, a different cDNA clone presumed to represent the mouse homolog of human AML1 (PEBP2 alpha B) was isolated from a cDNA library derived from B cells. The deduced amino acid sequence of PEBP2 alpha B is 99% identical to that of AML1 for the first 241 residues, including the runt homology region, though their sequences diverge thereafter. On the other hand, PEBP2 alpha B and PEBP2 alpha share only 92% and 82% homologies at the amino acid and nucleotide levels respectively, even for the runt homology region, indicating that these proteins are encoded by distinct genes. While PEBP2 alpha is highly expressed in T-cell lines but not in most of the B-cell lines and functions as an activator of T-cell-specific genes, PEBP2 alpha B is expressed in both types of cells. A possible functional relationship between PEBP2 alpha and PEBP2 alpha B is discussed in relation to leukemogenic potential of AML1.