The interaction between different morphine derivatives (morphine, codeine, N-methyl-morphine, N-methyl-codeine) and alpha-L-dipalmitoyl phosphatidylcholine (DPPC) liposomes was studied with differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR) spectroscopy. Small unilamellar DPPC-liposomes with the given morphine-derivative were prepared by sonication. The size distribution of liposomes was checked by dynamic light scattering (DLS). The amount of entrapped morphine was determined spectrophotometrically. Our results indicate that the morphine and its derivatives principally interact with the lipid head groups, and this interaction leads to a decrease in the mobility of the polar head groups, especially in case of codeine and N-methyl-codeine.