The functions of VLA-1 (CD49a, alpha 1 beta 1 integrin), a potential ECM protein receptor on activated human T lymphocytes in vivo, were investigated. Within a panel of 25 long-term cultured IL-2-dependent T cell lines, tau delta and CD8+ alpha beta cells expressed significantly higher levels of alpha 1 beta 1 than CD4+ alpha beta cells. While VLA-1-high tau delta or CD8+ cells adhered to plastic wells coated with collagen IV, collagen I, or fibronectin, moAb 1B3.1 to VLA-1 only inhibited the adherence to collagen IV. tau delta and CD8+ VLA-1-high T cells layered upon collagen IV in the presence of Mg2+ also spread elongated cytoplasmic extensions, which were abrogated by moAb 1B3.1. In contrast, spreading on fibronectin or spontaneous non-ECM-related spreading were not inhibited. Crosslinking of surface VLA-1 molecules with plastic-bound moAb 1B3.1 selectively induced expression of IL-2R on two of six VLA-1+ clones, both of which expressed tau delta TCR. Thus, CD49a is a specific collagen IV receptor in VLA-1-high tau delta and CD8+ alpha beta cells and can transmit signals to these lymphocytes to spread and express IL-2R.