We studied the prevalence and nature of immunoglobulin abnormalities in HIV-1-infected patients in the era of highly active antiretroviral therapy. Protein electrophoreses (PEP) were performed on and quantitative immunoglobulin levels obtained in samples from 320 consecutive HIV-1-infected patients. Samples with possible PEP abnormalities underwent immunofixation. The PEP pattern was normal in 83.8% of samples, 8.1% had subtle oligoclonal banding, and 4.4% had a low-concentration (<5% of total protein) monoclonal band. Hypogammaglobulinemia and polyclonal hypergammaglobulinemia accounted for 1.9% each. In multivariate analysis, younger age (odds ratio [OR], 1.06 with each decreasing year of life; 95% confidence interval [CI], 1.02-1.11; P = .016), female sex (OR, 2.4; 95% CI, 1.13-5.11; P = .02), viral load (OR, 1.50 with each increasing logarithmic viral load of 1.0; 95% CI, 1.14-1.98; P = .004), and CD4 cell count (> or =350 vs <350/microL [0.35 x 10(9)/L]) (OR, 2.71; 95% CI, 1.09-6.75; P = .032) were associated with monoclonal or oligoclonal banding. These results suggest that younger HIV-1-infected patients with a more robust immune system (higher CD4 cell count), which is stimulated by uncontrolled viremia, are most likely to have an augmented B-cell response to HIV infection. One manifestation of this B-cell response is low-concentration monoclonal banding in 4.4% of the patients studied.