The production of plasma proteins has been monitored in somatic cell hybrids between a rat hepatoma cell line (7777) and human fetal liver cells. Production of 14 plasma proteins was assayed in concentrated serum-free culture supernatants by electroimmunoassay. Alpha 2HS-glycoprotein (AHSG) was produced by 10 of 19 hybrids; concordancy for presence or absence of protein production was 100% for human chromosome 3. Orosomucoid (ORM) was produced in 8 of 19 hybrids, with a concordancy for presence or absence of protein of 94.7% with human chromosome 9. The chromosome location for genes for these two proteins, previously assigned by linkage studies, is confirmed by direct assignment. These studies have also suggested possible chromosomal assignments for loci for alpha 1-antichymotrypsin and C1 esterase inhibitor. Other genes for proteins which could not be assigned to specific chromosomes using these hybrids were: complement C3, ceruloplasmin, hemopexin, inter-alpha-trypsin inhibitor, prealbumin, retinol-binding protein, transferrin and apolipoproteins CII, B, and sinking-pre-beta [Lp(a)].