The nuclear proto-oncogene c-myc is believed to play a regulatory role in eukaryotic cellular growth and differentiation. Several studies have demonstrated rapid down-regulation of the steady-state levels of c-myc RNA during DMSO induced differentiation of the human 'promyelocytic' cell line, HL-60. However, little is known about the effect of DMSO on c-myc regulation in cells which are not induced to differentiate by DMSO. We have examined the effect of DMSO on c-myc RNA levels in a number of cell lines with different lesions in the c-myc gene, including those which do not differentiate in response to DMSO treatment. Here we demonstrate that DMSO induces a rapid, but transient, reduction in the steady-state level of c-myc RNA in human 'erythroid' K562 cells, Burkitt lymphoma lines Daudi and Raji, human T cell lymphoblastoid line CEM and mouse lymphoma line L1210. However, DMSO treatment does not produce a similar effect in the human colon adenocarcinoma cell line COLO 320 or HeLa epithelial cervical carcinoma cells. These observations demonstrate that the DMSO induced modulation of c-myc RNA levels is a more common phenomenon than previously recognised, and is not necessarily correlated with either the induction of cellular differentiation or growth arrest.