T-cells are activated by T-cell receptor (TCR) interaction with MHC-peptide complexes on antigen presenting cells. In the contact zone the immunological synapse (IS), a tight connection between the two cells, is formed, which is sustained from minutes through many hours. This is required for an appropriate T-cell activation resulting in cytokine secretion, proliferation or apoptosis. Clonal T-cell expansion is a central process of the adaptive immune response whereas apoptosis of activated T-cells is required to avoid chronic inflammation. Here we analyze the Ca2+ dependence of proliferation and apoptosis in primary human CD4+ T-cells following IS formation using anti-CD3/anti- CD28 coated beads. We found that the IS is much more efficient to stimulate IL-2 production and proliferation than non-focal TCR-stimuli. Surprising little Ca2+ entry through Ca2+ channels, which induced only transient [Ca2+ ]i elevations from 30 nM to 120 nM, was sufficient for maximal proliferation. We also show that proliferation is very Ca2+ sensitive in the range between 90-120 nM, whereas apoptosis is basically constant for the same [Ca2+ ]i levels. We conclude that very small changes in [Ca2+ ]i can dramatically change the ratio between proliferation and apoptosis and thus discriminate between overshooting and inefficient immune responses.