Three nonsteroidal anti-inflammatory oxicam drugs, namely meloxicam, piroxicam, and tenoxicam, were used to modify the properties of monomolecular films formed with 1,2-dilauroyl-sn-glycero-3-phosphocholine, 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine, or 1,2-dilauroyl-sn-glycero-3-phospho-(1-rac-glycerol). These systems were examined via surface pressure and surface electrical potential measurements, polarization modulation infrared reflection absorption spectroscopy, and Brewster angle microscopy. Moreover, phospholipase A2 activity was used to differentiate between the three drugs. Our results reveal that the oxicams studied modify membrane properties, namely hydration of the lipid polar heads, orientation of the molecules, and morphology of the domains. Phospholipase A2 was shown to be sensitive to the presence of the drugs in the systems studied; the activity of the enzyme correlates with the effect of meloxicam, piroxicam, and tenoxicam on the monolayer properties. The latter indicates that the anti-inflammatory action of oxicams may be related to interference with phospholipase activity in inhibition. addition to cyclooxygenase