We have studied the expression of several characterized genes during induction of mouse erythroleukemia (MEL) cells with dimethyl sulfoxide (DMSO) and have observed a specific pattern of changes in transcriptional activity and steady-state RNA levels associated with erythroid differentiation. During induction there is a gradual, steady decrease in total transcriptional activity and RNA content per cell, which by day 3 of DMSO treatment amounts to less than 50% of the level in the uninduced cell. During this time we observe increases in transcriptional activity for 5-aminolevulinic acid synthase, carbonic anhydrase form II, and band 3 coordinate with the large increase in beta-globin gene transcription. The results also demonstrate an early decrease in transcription for carbonic anhydrase form I, which precedes decreases in transcription for glyceraldehyde phosphate dehydrogenase and rRNA genes. Changes in steady-state RNA levels reflected changes in transcriptional activity during induction except for carbonic anhydrase II mRNA. These results represent the first report characterizing the regulated expression at transcriptional and posttranscriptional levels of several known genes that are characteristically expressed in the erythrocyte. The results demonstrate that coordinate gene expression in erythroid differentiation occurs primarily at the level of transcription.