Circulating immune complexes have been shown to be common in rheumatoid disease and to relate to severe systemic manifestations of disease. Hypocomplementaemia and complexes detected by anticomplementary activity are found in systemic rheumatoid vasculitis and in other complications such as Felty's syndrome. By contrast elevated complement levels and complexes detected by platelet aggregating activity are common in early and in continuing active rheumatoid disease. The common presence of circulating immune complexes suggests some therapeutic manoeuvres which might be helpful in systemic rheumatoid disease. Direct attempts to alter the levels of complexes by plasmapheresis, an effective treatment for acute exacerbations of systemic lupus erythematosus (SLE), have been disappointing in rheumatoid disease. Treatment with penicillamine and with cyclophosphamide may be effective in systemic manifestations and alter the levels of circulating immune complexes. An interesting paradox exists with penicillamine which may also induce a nephropathy with all the features of an immune complex deposition disease. The mechanism may relate to an alteration in the type of immune complex circulating, with a loss of the "protective" effect of rheumatoid factor.