Beta 2-microglobulin (beta 2-M) levels were determined in the serum of 24 patients treated with high-dose human recombinant interferon-alpha (IFN alpha) for AIDS-associated Kaposi's sarcoma. There was a significant increase in serum beta 2-M levels, irrespective of the response to treatment. However, the increase of serum beta 2-M levels in responders appeared to be more pronounced than in those with progressive disease, but this difference was not significant. The increase was only found during the initial 8 weeks; thereafter, beta 2-M levels declined in patients with continuing clinical improvement during ongoing treatment with IFN alpha. This may have been related to IFN alpha dose modification at 8 weeks for all patients. The initial rise in serum beta 2-M might be related to the immunomodulation properties of IFN alpha. Because serum beta 2-M levels were also enhanced in non-responders, this rise does not demonstrate that immunomodulation by IFN alpha is a mechanism of anti-tumour activity in AIDS-associated Kaposi's sarcoma.