Relapsing polychondritis is a rare autoimmune disease characterized by inflammation and degeneration of cartilaginous tissue. We describe the first reported cases of relapsing polychondritis in patients with human immunodeficiency virus (HIV) and no associated connective tissue diseases. The relationship between autoimmune and HIV diseases is complex and unclear. Treatment of HIV disease with antiretroviral therapy and subsequent immune restoration may lead to the development of autoimmune diseases in genetically susceptible individuals.