We have observed many patients with AIDS who have unexplained marked elevations in serum alkaline phosphatase. To determine the frequency of alkaline phosphatase elevations in patients with AIDS, and to identify diagnoses, medications, and demographic factors associated with such elevations, we conducted a retrospective study of the first 90 consecutive AIDS cases in hospitals affiliated with the University of Colorado Health Sciences Center in Denver, Colorado. We found elevations of alkaline phosphatase in excess of 1,000 IU/L in 17% of consecutive patients with AIDS. This level of elevation was less frequent in patients with Kaposi's sarcoma but there was otherwise no significant association with diagnoses or medications, or transmission categories for AIDS. The majority of the patients with elevations to this level did not have documented opportunistic infections or biliary tract dilatation previously described in the "cholangitis" syndrome in AIDS patients. Other explanations for these elevations for this common laboratory finding may exist.