We examined the effect of a nonsteroidal anti-inflammatory drug (NSAID), piroxicam, on apoptosis and matrix metalloproteinase 2 (MMP-2) activity compared with diclofenac and dexamethasone. The fibrosarcoma (WEHI-164) cell line was used to assess tolerability, MMP-2 activity and apoptosis. Piroxicam, dexamethasone and diclofenac were used at concentrations of 10-200 microg/ml in triplicate and 2-fold dilutions. MMP-2 activity was assessed using zymography. For assessment of apoptosis, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used. The results of this study show that piroxicam is able to diminish MMP-2 activity and induce apoptosis under in vitro conditions. Piroxicam also showed high tolerability compared with diclofenac and dexamethasone. In conclusion, piroxicam is able to induce apoptosis and suppress MMP-2 activity.