The c-fos proto-oncogene and H-2K class I major histocompatibility antigens are differentially expressed in low-metastatic Lewis lung carcinoma clones, but not in high-metastatic clones. Interferons induce mRNA expression of fos and H-2 in non-expressor cells and elevate mRNA steady state levels of expressor cells. Transfection of non-expressor cells by v-fos or c-fos genes induces the transcription of H-2K mRNA and elevates the levels of H-2 proteins, but not of other gene products. These results, correlated with observations in other cell systems, suggest that the c-fos proto-oncogene controls the expression of MHC genes coding for class 1 antigens.