IFN-γ protects the synovial joint from degenerative articular changes in early experimental arthritis. Mono-articular antigen-induced arthritis (AIA) was triggered in mice previously immunized against methylated bovine serum albumin (mBSA); arthritis was induced after an intra-articular (i.a.) injection of mBSA. Changes in joint architecture were measured histologically in joint tissue sections from IFN-γ+/+ (n = 8) and age matched IFN-γ-/- (n = 10) three days after AIA induction. (A). Individual parameters of arthritis severity were determined from H&E stained arthritic knee joints; (mean ± SEM) reported; *P < 0.01. IL-1β expression was visualised in arthritic joints excised three days post AIA induction using cytokine specific immunohistochemistry. (B) and (C). Representative paraffin wax sections from IFN-γ+/+ and IFN-γ-/- stained for IL-1β (original magnification ×40). Negligible IL-1β staining observed in synovial tissues from IFN-γ+/+ mice (B). In IFN-γ-/- mice (C) intense IL-1β staining often seen in the pannus (denoted by red block arrows); articular cartilage frequently found damaged with surface fibrillation and clefts extending into transitional zone (denoted by black block arrows). Serial sections were stained with Safranin-O/Fast green. Cartilage depth and the depth of GAG depletion were calculated for each mouse from an average of five fields per femoral head. (D). Mean ± SEM depths in μm reported for IFN-γ+/+ and IFN-γ-/- (*P < 0.01). (E). Representative Safranin-O/Fast green stained para-sagittal section from IFN-γ-/- demonstrating severe GAG depletion (block arrows) and reduced cellularity. (F). Corresponding section from a IFN-γ+/+ knee joint, minimal GAG depletion observed in the cartilage on the articular surfaces (original magnification ×20).