4 types of immune complexes according to the Heidelberger curve were prepared as an in vitro model for immune complexes in rheumatoid arthritis and collagen diseases. Immune complexes of high and moderate antigen excess and immune complexes of high and moderate antibody excess were incubated with increasing concentrations of a mixture of enzymes or papain or pancreatin. The concentration of immune complexes was determined by a solid phase C1q radioimmunoassay before and after incubation. Up to 90% of the complexes of antigen excess were disintegrated even by low doses of enzymes (5-10 mg%); total cleavage appeared at 80 mg% enzyme concentration. Complexes of the antibody excess zone were gradually disintegrated by enzyme concentrations gradually increasing from 5 to 80 mg%, where total cleavage appeared. Single enzymes showed less cleavage activity than enzyme mixtures. Although enzymes were administered to supernatants of the Heidelberger precipitation containing soluble immune complexes as well as enzyme inhibitors, enzymatic activity was not impaired and immune complexes were disintegrated. The results of these investigations are discussed in regard to treatment with enzymes.