The proteins synthesized by Friend erythroleukemic cells (clone 745), before and after they have been induced by treatment with dimethylsulfoxide to undergo overt erythroid maturation, have been analyzed by a number of biochemical methods. None of these techniques has, however, revealed any consistent observable differences (other than quantitative variations in the concentrations of particular proteins) between the “uninduced” and the “induced” cells. Thus, various classes of cellular proteins (whole cell, cytoplasmic, and nuclear) appear to be very similar in the two types of cells when analyzed by two-dimensional gel electrophoresis. Of particular interest is the finding that the strain-specific hemoglobins of DBA 2 mice (the line from which the Friend cells were derived by viral transformation) are being synthesized in both the uninduced and the induced cells but at apparently markedly different rates. A monospecific antibody preparation against purified DBA 2 mouse α- and β-globins was used to quantify the amount of these proteins in Friend cells during the course of dimethylsulfoxide-induced differentiation. Rocket gel immunoelectrophoresis, radial immunodiffusion analysis, and competitive radioimmunoassay revealed that the uninduced Friend cells contained, on the average, about 0.45 pg of hemoglobin per cell and this amount increased about 32-fold (to about 14.4 pg per cell) after 5 days of induction. Furthermore, use of the antibody preparation in indirect immunofluorescence studies revealed the constitutive synthesis of low levels of globins in virtually all of the uninduced, actively dividing, leukemia cells. These studies indicate that the standardly used benzidine staining method for detecting hemoglobins is insensitive for the detection of low levels of these proteins. The results of this study indicate that the cells in this particular leukemic population are, in reality, already “differentiated.” This suggests that the cells may represent an intermediate stage of erythroid maturation whose further progress along the normal in vivo terminal differentiation pathway has been blocked by viral transformation. Perhaps various “inducers,” such as dimethylsulfoxide, may enable these cells to partially overcome this block.