Although a normal or increased anion gap (AG) is commonly used to help assess acid-base balance, decreased AG has aided in the diagnosis of halogen ingestion and myeloma. Substantially increased levels of IgG cause a decrease in the AG. Patients with polyclonal increases in immunoglobulins, especially hepatic cirrhosis, also exhibit decreased anion gaps. Patients with human immunodeficiency virus (HIV) infection commonly show polyclonal increases in immunoglobulins. A case is reported of a patient with HIV infection who exhibited a decreased AG associated with increased polyclonal IgG (63 g per L). Unlike the electrophoretic profile of patients with hepatic cirrhosis, which commonly shows a beta-gamma-globulin bridge, reflecting a decreased immunoglobulin degradation, the profile of the patient with HIV infection was consistent with an increased immunoglobulin synthesis. Examination of sera from 18 additional HIV positive patients indicated that, in general, the AG of HIV infected patients with normal renal function is significantly higher than in normal persons. The significance of this finding is as yet unclear. Nevertheless, decreased AG was associated with increased IgG. This may complicate the use of the AG in evaluating HIV infected patients because of frequent elevations in IgG. These relationships are now in the process of further investigation. Nevertheless, it is suggested that, with appropriate history and physical, identification of a decreased anion gap in conjunction with a polyclonal increase in gamma-globulin may be reason to consider a work up for infection by HIV.