We report the presence of serum cryoimmunoglobulins in patients with attacks of a newly described epidemic arthritis--Lyme arthritis--and in some patients with a characteristic skin lesion--erythema chronicum migrans--that sometimes precedes the onset of the arthritis. Seven patients who had cryoimmunoglobulins at the time of the skin lesion have developed arthritis; four patients without them have not. The cryoglobulins in patients with the skin lesion consisted primarily of immunoglobulin M (IgM); those in patients with arthritis often included both IgM and IgG. These findings support the hypothesis that a common origin exists for the skin and joint lesions and suggest that circulating immune complexes may have a pathogenetic role in Lyme arthritis.