SUMMARYT-cell activation requires at least two signals: antigen and a costimulatory signal. As antigenpresenting cells play an important role in this area, the role of CD14+ cells in T-cell activation, proliferation and activation-induced cell death (AICD) was investigated. Using phytohaemagglutinin (PHA) activation, it was found that CD14 + cell depletion resulted in significantly greater AICD, decreased lymphocyte growth and up-regulated interleukin-2 (IL-2) secretion. However, T-cell activation was delayed according to the expression of CD69 and CD25. Dynabeads conjugated with anti-CD14 monoclonal antibody (mAb) bound CD14 + cells and induced secretion of IL-1b, tumour necrosis factor-a (TNF-a), transforming growth factor-b (TGF-b) and IL-6, but not IL-2, IL-12 or IL-15. Supernatants were collected from Dynabeads-activated CD14 + cell cultures and designated as 'CD14 cocktails'.Addition of CD14 cocktails to CD14 + cell-depleted mononuclear cell cultures reversed the increased AICD, decreased lymphocyte growth and increased IL-2 secretion. Depletion of IL-1b and TNF-a in the CD14 cocktails by panning followed by blocking with the corresponding mAbs had no effect on the active AICD protection. TGF-b was determined not to be the active factor owing to the presence of >1 . 0 ng of TGF-b in the media for culturing both CD14 + and CD14 x peripheral blood mononuclear cells (PBMC). The CD14 cocktails did not contain IL-12 and IL-15. Depletion of IL-6 with panning followed by blocking residual IL-6 with anti-IL-6 mAb significantly reduced the protective effect of the CD14 cocktails. Human recombinant IL-6 also partially reversed the effects of CD14 + cell depletion on AICD, lymphocyte growth and IL-2 secretion. The data suggest that IL-6 is one of the active factors in the survival signal from CD14 + cells.