The production of interleukin 1 (IL 1) and interleukin 2 (IL 2) by macrophages and lymphocytes from three animal models commonly used for rheumatoid arthritis, viz. adjuvant-induced and type II collagen-induced rat arthritis, and MRL/1 murine arthritis was studied. Although the peritoneal macrophages from adjuvant-arthritic rats in culture produced increased amounts of prostaglandin E2 (PGE2) and lower levels of IL 1 than the control group, cells from collagen-arthritic rats released normal levels of PGE2, but increased amounts of IL 1. After activation with lipopolysaccharides, the IL 1 production by macrophages from all groups was comparable. Addition of indomethacin did not significantly change the IL 1 production in any of these groups. In the absence of any exogenous mitogen, IL 2 production by the lymphocytes of adjuvant-arthritic rats was low, but could be restored to the normal levels when phytohemagglutinin A (PHA) or concanavalin A (Con A) was added. The lymphocytes from collagen-arthritic rats were capable of producing IL 2 without the need of any T cell mitogen. The lymphocytes from MRL/1 mice seemed to lack the functionality in terms of IL 2 production. The macrophagic IL 1 production in these animals was normal. Our data suggest that the type II collagen arthritis model may closely resemble human rheumatoid arthritis in which IL 1 and IL 2 production by the mononuclear cells is significantly enhanced.