Compared to a panel of healthy controls, sera from 13 of 23 (57%) patients with the acquired immune deficiency syndrome (AIDS) were shown to have elevated levels of circulating immune complexes (CIC) containing IgA. Levels of IgG-containing CIC were increased in seven patients (30%); no patients had elevated levels of IgM-containing CIC. Additional experiments showed that in all instances in which IgG CIC were demonstrable, IgA was also present; however, IgA CIC could be found that did not contain IgG. The IgA in the CIC was restricted to the IgA1 subclass. These data suggest selective abnormalities of IgA regulation in AIDS and raise questions as to the role in this disease of the immunoglobulin isotype usually thought to possess different protective mechanisms from those attributed to other isotypes.