Objective of this project was to determine whether synovial expression of interleukin-2 (IL-2) in arthritis is a disease-specific phenomenon. Immunohistological examination of needle biopsies from 7 rheumatoid arthritis (RA) patients never exposed to disease modifying antirheumatic drugs (DMARDs), 13 RA patients on DMARDs, 4 patients with seronegative spondyloarthritis (SpA), and 5 psoriatic arthritis (PsA) patients. Biopsies were either snap-frozen immediately or cultured for 48 hr, with and without phytohaemagglutinin (PHA) prior to APAAP staining. In snap-frozen biopsies, IL-2 was detected in none of 18 RA samples with significant T cell infiltrates. In contrast, IL-2 was seen in 7/9 PsA/SpA samples. After culture without PHA, IL-2 was detected in 0/14 RA and 5/6 PsA/SpA samples; with PHA, IL-2 was present in 1/14 RA and 2/2 PsA/SPA samples. Synovial IL-2 protein expression appears to distinguish between RA (absent) and PsA/SpA (present). This may reflect a difference in pathophysiology between these diseases.