Oxaprozin is a nonsteroidal anti-inflammatory drug characterised by a propionic acid-based structure. It is able to diffuse easily into inflamed synovial tissues after oral administration. Although discovered > 20 years ago, it is now under intensive investigation because of its unusual pharmacodynamic properties. Other than being a nonselective cyclooxygenase inhibitor, the drug is capable of inhibiting both anandamide hydrolase in neurons (median inhibitory concentration [IC50] = 85 micromol/l), with consequent potent analgesic activity, and NF-kappaB activation in inflammatory cells (IC50 = 50 micromol/l). Moreover, oxaprozin induces apoptosis of activated monocytes in a dose-dependent manner, with the effect being detectable at a concentration of 5 micromol/l and reaching the maximum activity at 50 micromol/l. As monocyte-macrophages and NF-kappaB pathways are crucial for synthesis of proinflammatory and histotoxic mediators in inflamed joints, oxaprozin appears to be endowed with pharmacodynamic properties exceeding those presently assumed as markers of classical nonsteroidal anti-inflammatory drug.