Human peripheral blood lymphocytes incubated in culture for 1 to 3 days at 37 degree C, but not at 4 degree C, release a soluble factor which can stimulate, up to 400-fold, collagenase production by isolated, adherent, rheumatoid synovial cells. Production of lymphocyte factor is enhanced by phytohemagglutinin or concanavalin A. By gel filtration the factor has an apparent molecular weight of about 12,000.