Long-term treatment of a murine retroviral-transformed cell line (Ki-Balb) with 50 units/ml of interferon (IFN) resulted in a morphological reversion. The effects of IFN on myc and Ki-ras oncogene expression were examined after 6 months of treatment. mRNA dot and Northern blots hybridization analysis reveal that the expression of c-myc at the RNA level decreases by about fourfold. This reduction in the c-myc mRNA appears to be selective since in the same cells v-Ki-ras and an endogenous retroviral gene, intracisternal A particles (IAP), are increased four- and threefold, respectively. No significant inhibition of cellular growth and cell-cycle distribution was observed in IFN-Ki-Balb-treated cells.