A block of RNA elongation in exon 1 of the murine c-myc gene has been described for normal mouse fibroblasts, lymphoid and myeloid cell lines and mouse erythroleukemia (MEL) cells. MEL cells differentiate after induction with the chemical agent dimethylsulfoxide (DMSO). The rapid initial down-regulation of c-myc that occurs after treatment with DMSO has been explained by an increase in the block of RNA elongation within the 3' part of c-myc exon 1. In contrast to these reports, we find that down-regulation of c-myc in DMSO-induced MEL cells occurs at the c-myc P1 and P2 promoters. The P1 promoter is repressed by inhibition of initiation, whereas transcription of P2 RNA is blocked by retention of RNA polymerase II at or close to the P2 promoter. The earlier described block of RNA elongation at a run of five thymidines in the 3' part of c-myc exon 1 was not observed.