Clonal lines of Friend murine erythroleukemia (F-MEL) cells have been generated following transfection with c-myc or c-myb expression plasmids. These clones produce high levels of abnormally regulated proto-oncogene transcripts and fail to terminally differentiate in the presence of dimethyl sulfoxide. To determine the relative levels at which the two proto-oncogenes might exert their inhibitory effects, we asked whether these clones could express differentiated functions in the absence of terminal differentiation. It was found that exposure of c-myc-transfected cells to hemin allows for the induction of hemoglobin, whereas c-myb-transfected cells were refractory to hemin induction. It thus appears that c-myb exerts a more globally suppressive effect on F-MEL-differentiated functions than does c-myc and may prevent the expression of those events that can otherwise be dissociated from the terminally differentiated state.