Immunohistological observations of synovial tissues obtained at the onset of rheumatoid arthritis (RA) are limited and often reflect the diagnostic confusion inherent in any study of early synovitis. However, a critical analysis of published information and the authors' experience allow certain preliminary conclusions. Synovial lining cell hyperplasia and mononuclear cell infiltration are conspicuous in the earliest examples of synovitis. The changes in RA, however, are indistinguishable from those of other inflammatory joint disease. Conventional T-cell phenotyping does not distinguish early from late synovitis. Mature CD4+ lymphocytes are the predominant cells in both situations, but the presence of B lymphocytes or plasma cells may have diagnostic or prognostic value. The relationship of lining cell hyperplasia to subintimal cell infiltration is not defined; whether they develop simultaneously or one precedes the other remains an important unanswered question. However, it is clear that production of enzymes (metalloproteinases) believed to be important in extracellular matrix destruction is an early event.