The object of this study was to determine the effects of eicosanoid precursor fatty acids on activation and proliferation of T lymphocytes from synovial fluid and synovial tissue of rheumatoid arthritis patients. Proliferation was determined by direct cell counts; phenotypic characterization of surfaces molecules was by cytofluorometric analysis. Dihomogammalinolenic acid, arachidonic acid, and eicosapentaenoic acid suppressed proliferation of interleukin-2-dependent lymphocytes by as much as 80%; cell viability was not altered by fatty acids. Administration of particular fatty acids may prove to be a useful therapeutic intervention in rheumatoid arthritis patients because of their ability to suppress activation and proliferation of synovial compartment T lymphocytes.