In 1991, gamma heavy chain disease was diagnosed in a 43-year-old female, who 3 years earlier had contracted an erosive seronegative chronic arthropathy. Her gamma heavy chain disease had a benign course, requiring no specific therapy for 5 years. In 1996, however, her lymphoproliferative disorder underwent a more malignant course, with renal and cardiac failure and increasing articular problems, requiring treatment with melphalan and prednisolone, following the protocol for myelomatosis. Laboratory studies revealed a monoclonal component in serum and urine. consistent with dimers of gamma-chains of the gamma3 subclass, but with a smaller molecular mass than normal gamma3-chains, suggesting molecular aberrations as consistently observed in this disorder. Massive localization of plasma cells and blasts with cytoplasmic or cell membrane staining for gamma3-chains, but no staining for kappa or lambda light chains, was observed by immunohistochemical studies of tissue specimens from bone marrow as well as affected synovial tissue. Large amounts of extracellular gamma3-chains were deposited in the synovial membrane. In addition, marked inflammatory changes with synovial cell hyperplasia were seen. Whether the present case represents primarily a gamma heavy chain deposition disease with reactive inflammatory changes in the joints, or another example of gamma heavy chain disease preceded by seronegative rheumatoid arthritis, remains elusive. Regardless, a possible pathogenic link between the two disease processes is an intriguing possibility.