The expression of proto-oncogenes involved in myelomonocytic differentiation was studied in 3 metastatic murine lympho-macrophage hybrids (ESb, EbF1, EbF2-C4) which display several antigenic and functional macrophage properties. Constitutive expressions of fos and fesmRNA, which were not detectable in the weakly metastatic parent lymphoma (Eb), was shown in all the proliferating hybrid lines. By contrast, c-myc and c-myc expressions were shared by the tumor parent and the hybrids. The c-fos transcripts observed in the hybrids were atypical in size, 2.3 kb, but standard 2.2-kb transcripts could be detected in serum-induced cells, even in the non-expressing Eb lymphoma. The kinetics of the induced fos mRNA was found to conform to the features reported in the literature for a large variety of cells. No structural alteration of the c-fos gene was detected by Southern analysis. PCR amplification of the 2.3- and 2.2-kb fos mRNA showed that they are identical in size in both the coding and the 3' untranscribed region. A longer poly A tail is thought to account for the additional 100 bp in the 2.3-kb fos mRNA, as both the 2.3- and 2.2-kb transcripts attain the same size following de-adenylation.