Hyperviscosity syndrome secondary to hypergammaglobulinemia is a rare and potentially fatal complication in patients with human immunodeficiency virus type-1 (HIV-1) infection. We studied an HIV-1-positive patient with symptomatic hyperviscosity attributable to IgG(1)kappa multiple myeloma. The patient initially responded to plasmapheresis and was subsequently treated with cytotoxic immunosuppressive chemotherapy. The patient remained asymptomatic during a 3-year follow-up period. The monoclonal IgG(1)kappa gammopathy evolved to a biclonal variant of the same subtype with an expansion of marrow plasma cell population. Western blot analysis demonstrated that this myeloma-associated paraprotein was strongly reactive against the HIV-1 p24 gag antigen.