Polyethylene glycol precipitation assays (PEG-A) have been promoted as technically simple, inexpensive methods for detecting and quantitating circulating immune complexes; however, their specificity and sensitivity have not been clearly defined. Data are presented showing that the percent recovery of IgG in 3.5% PEG increases as the concentration of IgG increases such that hypergammaglobulinemia alone can cause a positive test result. When sera from 25 patients with rheumatoid arthritis were studied, no correlations were found between results obtained by either Raji cell assay, or cryoprecipitation and those obtained by PEG-A. We conclude that 3.5% PEG-A, although appealing because of simplicity, can not be used as a substitute for established, but technically more demanding assays for circulating immune complexes.