Peripheral blood leukocytes (PBL) from patients with rheumatoid arthritis (RA) and from control subjects were exposed to rheumatoid and osteoarthritic synovial membrane extracts. The number of nonadherent PBL in the presence of each extract was monitored in a test tube leukocyte adherence inhibition (LAI) assay. Six of 7 rheumatoid synovial extracts produced significantly greater nonadherence values when RA leukocytes were used as the test cell (36 +/- 5) compared with values obtained when control leukocytes were used (-5 +/- 3). Preincubation of LAI reactive leukocytes from RA patients with the RA synovial extracts abrogated the positive response, whereas preincubation with the OA extract had no effect. These studies indicate that leukocytes from RA subjects respond to a greater degree to extracts derived from rheumatoid synovium than to extracts derived from osteoarthritic synovium and add further support to the concept that unique substances (putative neoantigens?) are present in RA synovium.