Recently we reported that polymorphonuclear leucocyte (PMNL) migration in vitro through a barrier of human synovial fibroblasts (HSF) involves both β₂ (CD18) and β₁ (CD29) integrins on the PMNL. Here we investigated the role of the β₂ integrin family members, lymphocyte function‐associated (LFA)‐1 (α_Lβ₂ or CD11a/CD18) and Mac‐1 (α_Mβ₂ or CD11b/CD18), in PMNL migration through HSF and human dermal fibroblast (HDF) monolayers. Treatment of PMNL with monoclonal antibody (mAb) to LFA‐1 (anti‐α_L) did not inhibit PMNL migration through either monolayer in response to C5a. In contrast, mAb to Mac‐1 (CD11b) inhibited (by 30–40%) PMNL migration, and by virtually the same extent as mAb to the β₂ integrin chain (CD18) (40% inhibition). Addition of mAb to LFA‐1 to mAb to Mac‐1 did not result in greater inhibition. This was in contrast to PMNL migration through human umbilical vein endothelium (HUVE) monolayers, where mAb to LFA‐1 or to Mac‐1 each partially inhibited PMNL transendothelial migration, and when these mAbs were combined, synergistic inhibition of migration was observed, reaching 90–95% inhibition. Intercellular adhesion molecule 1 (ICAM‐1) was not required for Mac‐1 mediated migration through HSF or HDF, because treatment of the fibroblasts with mAb R6.5 (F(ab)₂) to ICAM‐1, which blocks the Mac‐1 binding site on ICAM‐1, did not inhibit PMNL migration. An LFA‐1–ICAM‐1 mechanism of PMNL migration through HSF and HDF monolayers could be detected after treatment (4 hr) of the monolayers with TNF‐α plus IFN‐γ, which upregulated ICAM‐1 on the fibroblasts. The results demonstrate the β₂ integrin dependent PMNL migration in connective tissue may involve primarily Mac‐1, with little involvement of LFA‐1 or ICAM‐1, a situation in marked contrast to PMNL migration across endothelium. However, in inflammatory conditions in which TNF‐α and/or IFN‐γ may be generated, a role for LFA‐1–ICAM‐1 may be induced.