The changes occurring in the pattern of genes expressed at the polysomal level during induction of Friend cell differentiation with 1.5% dimethylsulfoxide (DMSO) have been examined in two ways. First, homologous and heterologous hybridization experiments between cDNA and polysomal poly(A)+ mRNA from differentiated and undifferentiated cells show that about 8000 mRNAs are expressed at both stages of differentiation, the major change being the accumulation of α+β-globin mRNA after DMSO treatment. The vast majority of the mRNA sequences do not change qualitatively, remaining homologous between the undifferentiated and differentiated state. However, in addition to the accumulation of α+β-globin mRNA there is a decrease, after DMSO treatment, in the concentration of abundant and semiabundant sequences found in undifferentiated cells. From control studies with Friend cell variants and fractionated cDNA probes enriched in these sequences, it is shown that the decrease in the abundance of these mRNAs is related to the process of differentiation and not an artefact of DMSO treatment. Comparison of the polysomal poly(A)+ mRNAs in differentiated cells to those in pluripotential embryonal carcinoma (EC) cells shows that the vast majority of the sequences are homologous and hence not erythropoiesis specific. Second, comparison of these mRNA populations by in vitro translation and analysis of the protein products on two-dimensional gels also shows that among the more abundant proteins very few qualitatively new proteins appear after differentiation and that the majority are the same as those translated in EC mRNA. There are several proteins prominent in undifferentiated cells which diminish after DMSO treatment, in agreement with the findings from the cDNA studies. © 1979.