Immunoglobulin assays that are sensitive and specific for detecting human immunodeficiency virus type 1 (HIV-1) infection are especially important in developing countries where PCR and viral culture may not be readily available. Immunoglobulin E (IgE), which is elevated in HIV-1 infection, is the only antibody that does not cross the placenta, making it potentially valuable for viral detection in both children and adults. This study developed an assay for detection of HIV specific IgE antibodies in adults. A total of 170 serum samples from 170 adults (116 HIV positive and 54 HIV negative) were analyzed. Serum or plasma samples were treated by using the protein G affinity method. The HIV status was determined by using two IgG enzyme-linked immunosorbent assays (ELISAs) and one Western blot evaluation. The IgE enzyme immunoassay test for HIV-1 correctly identified the HIV status in 98.8% of the samples (168 of 170). One false-positive and one false-negative test occurred with the IgE ELISA, as well as with the IgG ELISA test but were correctly identified by the IgE test. Analysis of the data demonstrated a high specificity (99%) and sensitivity (99%) of the IgE test, with 95% confidence intervals. The IgE assay appears to be sensitive and specific, suggesting that IgE-specific antibodies offer an effective method to detect HIV-1 infection in adults.