The LFA‐1 adhesion molecule is involved in cell adhesion events of leukocytes through binding to ICAM‐1, ICAM‐2 and ICAM‐3. Whether binding to either of these ligands similarly affects co‐stimulation of T cells and cytokine secretion is unknown. We demonstrated that LFA‐1 co‐stimulation under suboptimal concentrations of anti‐CD3 monoclonal antibodies resulted in high, intermediate and weak proliferation of T cells on ICAM‐1, ‐2, and ‐3, respectively, which correlates with the distinct affinities of LFA‐1 for these ligands. Furthermore, we investigated whether binding to ICAM‐1, ‐2 or ‐3 induced different cytokine profiles, thus regulating T helper cell function. Granulocyte‐macrophage colony‐stimulating factor and IFN‐γ were secreted in high amounts, whereas IL‐2, IL‐4 and IL‐5 could not be detected. Interestingly, we observed that LFA‐1/ICAM‐1 co‐stimulation of T cells resulted in high production of the Th2 cytokine IL‐10 compared to ICAM‐2 or ICAM‐3 co‐stimulation. In contrast, ICAM‐2 and ICAM‐3 induced a much stronger secretion of the Th1 cytokine TNF‐α compared to LFA‐1/ICAM‐1 induced co‐stimulation, despite the lower proliferation rate. These results demonstrate that besides facilitating cell adhesion, LFA‐1 serves as a potent co‐stimulatory molecule by inducing different cytokine patterns depending on the ligand bound.