Abstract Chondrex, a major secretory protein of human chondrocytes and synovial fibroblasts, is increased in serum of patients with joint and cartilage disease. We have developed a sandwich-type ELISA for quantifying chondrex in serum. The interassay CVs were 2.8–3.7% and the average within-run and total CVs were 3.6% and 5.4%, respectively. The limit of detectability by linear dilution was 20 μg/L, recovery upon dilution was 102% ± 5%, and analytical recovery (of added analyte) was 98% ± 11%. The reference interval (central 90% interval) for chondrex in healthy adults was 25–95 μg/L. Chondrex values for patients with active rheumatoid arthritis or osteoarthritis were significantly greater than in healthy adults, inactive rheumatoid arthritis patients, and diabetes patients (P <0.05). In patients treated with disease-modifying antirheumatic drug therapy, decreasing chondrex values reflected the clinical improvement observed in responders, whereas the values were maintained or increased in nonresponders. In conclusion, chondrex may be a useful marker in the clinical investigation of arthritis.