Abstract Phospholipids are amphipatic molecules with long hydrophobic acyl chains and zwitterionic polar heads which assemble into different types of molecular aggregates. The most relevant is the bilayer because of its relation with cell membranes, which are very complex entities. For this reason, simpler molecular models based on phospholipids bilayers are widely used. We have determined the bilayer structure of phospholipids located in the outer and inner monolayers of most cell membranes, and use them as molecular models to study the way different chemicals of biological interest interact with cell membranes. We present the results of our studies on the nonsteroidal anti‐inflammatory drug diclofenac, from which little is known about its effects on human erythrocytes. This report presents the following evidence that diclofenac interacts with the human red cell membrane: a) X‐ray diffraction and fluorescence spectroscopy of phospholipids bilayers show that diclofenac interacts with a class of lipids found in the outer moiety of the erythrocyte membrane; b) in isolated unsealed human erythrocyte membranes the drug induced a disordering effect on the acyl chains of the membrane lipid bilayer; c) in scanning electron microscopy studies on human erythrocytes it was observed that the drug induced morphological changes different from their normal biconcave shape.