Sera from 105 adult patients with idiopathic chronic glomerulonephritis (GN) were investigated to assess the diagnostic and prognostic value of cryoglobulin (CG) detection. CG+ sera were found in 49% of cases but also in 34% of normal donors. CG composition in these two groups was different. Concentrations of CG greater than micron g/ml were considered as abnormal, since concentrations did not exceed this value in the controls. Using this criterion 30% of patients with GN had CG; most had membrano-proliferative GN, GN with mesangial IgA deposits, and membranous GN. CG occurred with the same frequency but at higher concentrations in the group of patients with diffuse proliferative GN than in other groups; however, there was no difference in the frequency and concentration of CG when GN was thought to be mediated by immune complexes (IC) than when it was not. No relationship was observed with disease activity. In conclusion low CG might represent an in vitro artifact of a common in vivo immunoregulatory mechanism in normal donors. Although they might be a marker for the presence of IC in adult patients with GN not related to systemic disease, CG detection appears to be of little help in diagnosis, assessment of disease activity, or therapeutic monitoring.