The authors investigated the presence of IgG-containing immune complexes in middle ear effusions as well as in middle ear mucosa and mastoid mucosa using the Raji cell radioimmunoassay (RIA), the inhibition of anti-antibody, and direct immunofluorescence tests. The Raji cell RIA showed positive results in two of 15 concentrated middle ear effusions but in none of 26 unconcentrated samples. The anti-antibody inhibition assay revealed immune complexes in two of 26 unconcentrated fluids. Thus, with two assays for soluble immune complexes, only four of 63 samples (6 per cent) were positive. Direct immunofluorescence of middle ear mucosa and mastoid mucosa resulted in localization of IgA and IgG in the plasma cells of the middle ear mucosa. A concomitant immunofluorescent staining for complement or immunoglobulin deposits along the basement membrane of the epithelium and/or blood vessels was not observed in 37 biopsy specimens. These findings do not support the concept that immune complexes are involved in the pathogenesis of otitis media with effusion.