Testing for human immunodeficiency virus (HIV) infection in patients with systemic lupus erythematosus (SLE) leads to a higher than expected rate of positive ELISA results and indeterminate Western blot results. Because most of these patients lack any risk factors for HIV infection and the coexistence of SLE and HIV infection is extremely rare, most of these results represent false-positives. Two cases of false-positive HIV tests are reported and the related literature is reviewed. Further, Celum's algorithm for evaluating indeterminate HIV Western blot tests, which is especially valuable in lupus patients, is discussed.