Complement C3, when its cDNA was transfected into COS-1 cells, was synthesized as a precursor, pro-C3, which was intracellularly processed into the α and β subunits, although not completely. A cDNA for rat α 1-protease inhibitor (α 1-PI) was mutated in vitro to encode its variant with the modified active site (Met 352→ Arg). In cells co-transfected with the mutant α 1-PI cDNA and the C3 cDNA, pro-C3 expressed was secreted without being processed into the subunits. Co-transfection of the mutant α 1-PI cDNA and the albumin cDNA also resulted in the inhibition of intracellular conversion of proalbumin into serum-type albumin. No inhibition of the processing of each proform was observed in cells co-transfected with the normal α 1-PI cDNA. Taken together, the results indicate that the α 1-PI variant (Met 352→ Arg) expressed inhibits specifically an intracellular enzyme which is involved in the proteolytic processing of both pro-C3 and proalbumin.