To determine whether interleukin-1 (IL-1) and interleukin-1 receptor antagonist (IL-1ra) are produced by different macrophage subsets, we applied immunoperoxidase and double-labelling immunofluorescence techniques to 10 rheumatoid arthritis (RA) and 10 osteoarthritis (OA) synovial membranes. In RA, greater numbers of early 27E10+ macrophages were found in the sublining layer while mature 25F9+ macrophages were more abundant in the lining layers. The majority of IL-1alpha+ cells were also IL-1ra+ (79 +/- 12% sublining layer, 98 +/- 2% lining layer). In OA sublining layer, a higher percentage of cells double stained for 25F9 and IL-1ra was detected compared to those double stained for 25F9 and IL-1alpha (P < 0.004). In OA, 25F9+ macrophages demonstrated a lower percentage of IL-1alpha+ in the lining and sublining layers compared to RA (P < 0.02 and P < 0.004, respectively). It may be concluded that once monocytes have migrated into the RA joint, they undergo phenotypic and functional changes from an early profile (27E10+, CD14+, low percentage of IL-1+ and IL-1ra+ cells) to a mature profile (CD14+/-, 25F9+, RM3/1+, high percentage of IL-1+ and IL-1ra+ cells).