Flare-up reactions were induced in the rat chronic antigen-induced arthritis model (AIA), similar to those in mice and rabbits. After two consecutive immunizations (500 micrograms each, Day -21 and -14) with methylated bovine serum albumin (mBSA) in complete Freund's adjuvant (CFA), a biphasic primary arthritis was induced on Day 0 by intra-articular (i.a.) injection of 100 micrograms mBSA. The acute arthritic phase lasted 1 week, followed by chronic, mild joint swelling. Flare-up could then be induced on Day 40 by a second i.a. injection of 10-100 micrograms mBSA into the knee, with maximal flare-up reaction 2 days following the i.a. injection, and a return to chronic levels within 2 weeks. On Day 6 after induction of the flare-up, the inflamed joint showed massive cartilage and bone destruction; high numbers of alpha beta-T-cell-receptor-positive cells and macrophages, but only a few IL-2-receptor-carrying cells were detected in the inflamed synovial membrane. Induction of a second flare-up, 40 days after the first one, was possible by i.a. injection of 100 micrograms mBSA. Unlike in the mouse model, intravenous injection of up to 10 mg mBSA failed to induce flare-ups in the chronically inflamed joint.