The use of porphyrin derivatives in photodynamic therapy is of excellent prospect for the treatment of superficial or easily reachable tumors. The selection of porphyrin derivatives by tumor cells depends to a large extent of their ability to interact with the biological membrane. The evaluation of porphyrin interaction with phospholipids can thus be used as a screening method. In this work we report on the assessment of the interaction of three new porphyrin derivatives with various phospholipids forming Langmuir films by surface tension and surface pressure measurements, grazing incidence X-ray diffraction, and liquid chromatography on an IAM stationary phase. The results show that the hydroxylated phenylporphyrin (M-THPP) is able to interact with all studied phospholipids and to significantly disorganize the structure of their monolayers. Obviously, the interaction occurs at the level of the hydrophobic chains of a phospholipid. A triglucoconjugated phenylporphyrin (m-TPP(Glu)(3)) also interacts with the phospholipids though to a lesser extent. Conversely, the tetraglucoconjugated derivative (m-TPP(Glu)(4)) exhibits both a weak surface activity and a poor affinity for the studied phospholipids. Thus, whereas m-THPP and m-TPP(Glu)(3) are expected to penetrate into a biological membrane, m-TPP(Glu)(4) seems unlikely to do so.