The expression of a number of proto-oncogenes (myc, erb B, Ha-ras, bas, rel, mos, sis, myb, ki-ras, fms, src and fos) was studied in developing rat liver. Northern blot hybridization shows that cellular counterpart of erb B, Ha-ras, and fos oncogenes were in an early stage of liver development, and the expressions of these proto-oncogenes gradually decreased as the liver developed, while c-myc transcript was found only in the rat fetal liver. The transcripts of these oncogenes were found in high level in Morris hepatoma 7777. Bas proto-oncogene was found in high expression at early stages of rat liver development but was not in hepatoma 7777. The expression of other proto-oncogenes studied (src, fm, rel, mos, sis, myb and ki-ras) did not change significantly during liver development and was almost the same in hepatoma and normal adult liver. Southern blot analysis demonstrates that gene amplification and apparent gene rearrangement were not responsible for the change in expression of erb B, Ha-ras, myc and fos proto-oncogenes. Our study gives further evidence that erb B, myc, Ha-ras and fos proto-oncogenes are involved in the control of cell growth and in the process of rat hepatocarcinogenesis.