The envelope protein of human immunodeficiency virus type 1 (HIV-1)--glycoprotein 120 (gp120)--has been demonstrated to dysregulate T cell function in vitro. We obtained autopsy tissues from individuals with chronic HIV-1 infection to determine whether there was enough gp120 in lymphoid tissues and/or blood to elicit these effects. We found that gp120 was present in high concentrations (>300 pg/mL) in the spleen and lymph nodes of some of these individuals. In contrast, very low amounts of gp120 and p24 were detected in all serum samples tested. These findings underpin the clinical relevance of nonentry functions of gp120 and the chronic nature of human immunodeficiency virus (HIV)-induced immune dysregulation.