Objective. Lymphotoxin  (LT), a cytokine produced by T cells and B cells, plays a central role in the normal development of lymph nodes and is critical in the formation of ectopic germinal center reactions in rheumatoid synovitis. Because resident fibroblast-like synoviocytes (FLS) express receptors for LT, we examined the consequences of FLS activation by LT.Methods. FLS from patients with rheumatoid arthritis were isolated and examined for the expression of LT receptor. FLS were incubated with LT␣12 and assayed for the production of cytokines and chemokines and the up-regulation of adhesion molecules.Results. Exposure of FLS to recombinant LT␣12 resulted in the production of multiple inflammatory cytokines and metalloproteinases, implicating FLS as amplifiers of the inflammatory process in the inflamed joint. Additionally, LT␣12 was found to up-regulate the expression of cell adhesion molecules, rendering FLS to efficient adhesion substrates for T cells. LT␣12 also induced production of the chemokines CCL2 and CCL5, which elicited transmigration activity of T cells. Upon stimulation with LT␣12, FLS did not acquire characteristics of follicular dendritic cells.Conclusion. These data document that FLS are involved in multiple stages of the inflammatory process, including the recruitment and retention of lymphocytes in the synovial microenvironment. We propose that the heterotypic interaction between LT-producing lymphocytes and responding FLS contributes to the establishment of complex lymphoid microstructures, and that this may be one element that defines susceptibility of the synovial membrane to lymphoid organogenesis.