Apoptosis of articular chondrocytes may play an important role in the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the incidence of chondrocyte apoptosis in equine articular cartilage (AC) specimens and examine the relationship between the process of cell death and the degree of cartilage degradation. The study comprised 2 populations of equine cartilage taken from the left forelimb. Population 1 (n=10) consisted of full depth cartilage from weight-bearing regions of equine metacarpophalangeal (MCP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints. Population 2 (n=9) comprised cartilage from 6 different regions of the MCP joint: dorsomedial, dorsolateral, centromedial, centrolateral, palmarome-dial and palmarolateral areas. Cartilage from each horse for each of the joints and joint regions was not always available. Seven micrometre cryostat sections were obtained. Haematoxylin and Eosin with Safranin-O stained sections were used to score structural differences between samples for features of cartilage pathology using a ‘modified’ Mankin scoring system. Two methods were used to quantify apoptotic chondrocytes: a direct method in which chondrocytes were assessed for morphological features of apoptosis using a light microscope and an immunohistochemical staining technique to detect the expression of active caspase-3 using a commercially available monoclonal antibody. Apoptosis assessed by the direct method did not show any association with increasing severity of OA (r=0.11, p=0.7205). Overall there was a positive correlation between caspase-3 expression and cartilage damage (r= 0.44, p=0.0043). Caspase-3 expression was found to increase linearly with increasing severity of OA in the superficial, middle and deep zones of AC (r=0.36, p=0.0198; r=0.49, p=0.0011 and r=0.37, p=0.0237 respectively). Moreover, caspase-3 expression was higher in the superficial and middle zones than in the deep zone (p<
0.001). In the superficial, middle and deep zones the expression of caspase-3 was higher in the MCP joint than the PIP joint (p<
0.05, p<
0.01 and p<
0.05 respectively). The significant positive correlation between disease severity and chondrocyte apoptosis, suggests that this process plays an important role in the pathogenesis of OA. The differences in the extent of apoptosis observed in different joints could be explained by the biomechanical environment of the joints.