Serum IgM and IgA rheumatoid factor (RF) levels were measured by ELISA in 71 adolescent and adult patients with cystic fibrosis (CF) and 69 control subjects. IgM RF values from 15 (21%) CF patients greater than 2 s.d. of control subjects (P less than 0.001). Elevated IgM RF values were significantly associated with worse spirometric measurements of pulmonary function (P less than 0.01) and with more frequent exacerbations of respiratory tract infection (P less than 0.001). A characteristic episodic arthropathy occurred in 27% of IgM RF positive patients, compared with 4% of IgM RF negative patients (P = 0.015). IgA RF values from 26 (37%) CF patients were elevated (P less than 0.001). Pulmonary function was significantly worse in patients with elevated IgA RF values (P less than 0.001). However, IgA RF was not associated with exacerbations of respiratory tract infection or episodic arthropathy. Both IgM and IgA RF values correlated significantly with their corresponding Ig levels, suggesting that RF synthesis was the result of polyclonal B cell activation. It is concluded that serum IgM RF values in CF are associated with worse lung disease and recurring bacterial antigenic stimulation. IgM RF may contribute to the development of arthropathy in some patients. Induction of IgA RF synthesis and its pathogenic potential may differ from IgM RF.