We have examined 11 patients with the acquired immunodeficiency syndrome (AIDS) for evidence of subclinical vitamin B12 malabsorption. Three subjects (27%) had low levels of vitamin B12. Eight subjects (73%), including these 3 subjects plus 5 others with normal vitamin B12 levels, had abnormal Schilling test results. In addition, 15% of an unselected population of 121 patients with AIDS and 7% of 27 patients without AIDS who were seropositive for human immunodeficiency virus type 1 (HIV-1) had low serum vitamin B12 levels. Stool cultures from the 8 subjects with abnormal Schilling test results revealed no pathogens. Intestinal involvement by Kaposi's sarcoma was found in only 1 patient. Biopsy specimens from 5 of 6 patients with vitamin B12 malabsorption, however, contained mononuclear cells harboring HIV-1, as indicated by in situ hybridization studies. Our observations suggest that vitamin B12 malabsorption is common in patients with AIDS and may be a very early manifestation of infection with HIV-1.