The adenovirus E1a oncogene has both positive and negative regulatory effects on the expression of a variety of host genes. Both type of effects have been reported for certain cell cycle genes such as c-myc. To study the potential role of c-myc in adenovirus transformation, we have assessed the steady-state levels of c-myc mRNA after serum stimulation in genetically related transformed or non-transformed cell lines in the presence or absence of E1a. Serum stimulated the accumulation of stable c-myc mRNA only in cell lines which did not express E1a. Therefore under the present assay conditions, E1a had a negative effect on the steady-state level of c-myc mRNA. Surprisingly, this effect was independent of the transformed phenotype.