Virus‐specific cytotoxic T lymphocytes (CTL) play a crucial role in modulating an immune response against human immunodeficiency type 1 (HIV‐1) infection. The generation of effector cytotoxic cells from CTL precursors involves intricate interactions with antigen via T cell receptors (TcR) and soluble cytokines. Interleukin (IL)‐7 can affect T cell maturation and differentiation. Here we report on a group of five HIV‐1‐positive individuals who tested negative for env‐and gag‐specific CTL activity. When exogenous recombinant human IL‐7 was added as a stimulus to the cultures, none (0/5) of the CTL‐negative individuals exhibited a CTL response. Individuals that were negative for HIV‐1‐specific CTL activity were found to lack IL‐7 receptor (IL‐7R) on CD8⁺ cells with a comparable reduction on CD4⁺ cells. Increased shedding of IL‐7R in the culture supernatant was observed. A significant reduction in receptor number was detected by binding of ¹²⁵I‐labeled IL‐7 and Scatchard analysis. The lack of IL‐7R is probably not due to endogenous IL‐7, since it was not detectable in the culture supernatants of the patients studied. HIV‐1 proteins may cause down‐modulation of IL‐7R expression, either by producing an insufficient number of molecules or by rapid decay of IL‐7R on T cells. These changes may alter the cells' capability to respond to the IL‐7 growth signal, resulting in CTL failure and subsequent mishandling of the virus.