AbstractWe have previously shown that streptococcal product (SP) extracted from the culture supernatants ofStreptococcus pyogenesATCC 19615 augments NK activity, partly by inducing the release of soluble factors from mononuclear cells. In this study we use SP as an NK stimulant to investigate the mechanism of NK depression in AIDS.We demonstrate that the NK activity of AIDS patients is lower than normal controls and can be significantly enhanced with SP, although not to control levels. The decreased cytotoxicity in AIDS is not due to a depletion of NK cells, nor to the depletion of lymphokines from CD4 cells that are directly involved in NK cell activation. PBMCs from patients with AIDS respond to SP, producing normal levels of NK‐en‐hancing substances in their supernatants. However, upon examining the ability of SP‐induced supernatants from control cells to augment the NK activity of cells from AIDS patients, we find significantly less activity in AIDS cells than in control cells, suggesting an intrinsic effector dysfunction of NK cells in