beta 2-Microglobulin (beta 2M) is a low-molecular-weight protein present in serum and other fluids during various autoimmune or chronic inflammatory diseases. beta 2-Microglobulin was measured in middle ear effusion (MEE) and serum samples obtained from 36 patients with chronic otitis media with effusion. Using a quantitative competitive enzyme immunoassay, we were able to demonstrate beta 2M in 98% of the MEE samples. The mean concentration of beta 2M was higher in the MEE samples than in the serum samples. There was considerable variability between ears in those patients with bilateral MEE. There was no correlation between beta 2M concentration and the patients' age, sex, MEE type, and culture results, or cytologic profiles of the MEEs. This increased beta 2M may reflect earlier lymphocyte activity during the inflammatory process.