Estradiol valerate did not ameliorate experimentally induced osteoarthritis in the rabbit. Both normal and osteoarthritic cartilage were susceptible to estradiol suppression of proteoglycan synthesis. Protoeglycan concentration was not diminished with estradiol, suggesting estradiol suppression of proteoglycan catabolism. The severity of osteoarthritis was unchanged despite markedly decreased proteoglycan catabolism. The severity of osteoarthritis was unchanged despite markedly decreased protoeglycan synthesis in the estrogen treated animals. Osteophyte proteoglycan metabolism differed from other osteoarthritic lesions. Differences in the metabolism of femoral and tibial articular cartilage were observed.