Stimulated by reports of an inhibitory effect of non-steroid anti-inflammatory drugs on fracture healing and heterotopic bone formation in clinical and experimental studies, this investigation was performed to study the effect of indomethacin on chondrogenesis and mineralization in vitro by chicken mesenchymal limb-bud cells. Limb-bud cell cultures were treated with indomethacin and, in order to study a possible effect of metabolites, with serum from indomethacin-treated rats. No effects of the drug on chondrogenesis, as estimated by staining with alcian blue, could be detected. This was also the case when mineralization in the cultures induced by high phosphate concentrations was studied. It is concluded that indomethacin probably exerts its effect on bone metabolism through mechanisms other than modulation of cell differentiation or cell proliferation.