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The mechanisms underlying the contraction-dependent apoptosis of primary fibroblasts are of prime importance in understanding anchorage-dependent survival/apoptosis of dermal fibroblasts. As integrins are essential extracellular matrix receptors in fibroblasts, their role in anchorage-dependent apoptosis/survival of fibroblasts was analyzed. Primary human fibroblasts displayed a marked reduction of apoptosis in mechanically relaxed collagen matrices in the presence of adhesion-blocking antibodies against α₁β₁ or α₂β₁. Anti-α_vβ₃ antibodies had a considerably weaker effect. In additional experiments RD cells, which lack α₂ integrin, displayed no apoptosis in mechanically relaxed collagen matrices. Their susceptibility to apoptosis was restored after transfection with functional α₂ integrin, and it could be blocked again by adhesion-blocking antibodies against α₂β₁ integrin. Therefore we conclude that …