Abstract We have examined certain aspects of IgG biosynthesis by constructing hybrids between MPC11 (γ2b, κ) and MOPC 315 (α, λ2) that have lost the ability to synthesize one or the other heavy chain. Cells express the three chains in a stable fashion, and both autologous (parental) and heterologous (nonparental) H and L chain pairs form and are secreted. The α H chain was found in polymeric form when associated with the heterologous κ L chain. The λ2 L chain covalently assembled to the heterologous γ2b H chain. Surprisingly, autologous pairing was always favored over heterologous pairing in vivo by 5 to 10:1 in terms of rate of assembly. Similar ratios were maintained in the secreted protein. These results suggest that co-expression of particular H and L chain pairs is predetermined. Evolution presumably operates to improve antigen recognition as well as rate of assembly of active molecules.