Cytokine expression was investigated in synovial cell cultures isolated from diseased joints of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Tumour necrosis factor alpha (TNF alpha) was produced spontaneously at high levels by both RA and OA synovial cells. There was no correlation between cell composition and level of TNF alpha produced. In contrast, lymphotoxin (LT) and Interferon gamma (IFN gamma) (greater than 50 pg/ml) were not found. This was further investigated in the RA cultures at both the mRNA and protein level. The results indicated that high levels of mRNA were produced spontaneously by these cells, but the relevant protein was undetectable. The presence of inhibitors and/or shed receptor is unlikely to account for undetectable LT as most of the recombinant LT added to the cultures could be recovered. In addition, in some cases this resulted in an increase in IL-1 production indicating that LT is biologically active in this system. It is not clear at this stage why the protein for these mediators (produced by activated T cells) are not found in the rheumatoid cultures, although it may be due to a post-transcriptional mechanism. This possibility is currently being investigated in addition to the development of more sensitive assays for these cytokines.