c-myb is expressed predominantly in proliferating immature hemopoietic cells and, like v-myb, functions as a transcriptional activator that displays sequence-specific DNA binding. Oncogenic activation of the c-myb protein (Myb) is associated with carboxyl-terminal and/or amino-terminal truncations, the former of which also potentiates Myb's transcriptional activation capacity. We show here that a carboxyl-truncated Myb protein binds with a 7-fold higher affinity to an oligonucleotide bearing a Myb recognition sequence than does the full-length form. In addition, data are presented which show that Myb binds with different apparent affinities to variants of the recognition site and that Myb binds independently to adjacent sites regardless of the orientation of these sites.