A case report of rheumatoid arthritis developing during alpha-interferon therapy of chronic hepatitis C is reported. The rheumatoid arthritis was severe, being non-responsive to the use of nonsteroidal anti-inflammatory drugs, and persisted despite discontinuation of the interferon therapy. The literature relative to this case suggesting an association between rheumatoid arthritis and interferon therapy is presented. This case suggests that interferon therapy may precipitate subclinical rheumatoid arthritis in an individual without pre-existing clinical arthritis.