The acid–base properties of Zn-hematoporphyrin IX (ZnHP) and Zn-mesoporphyrin IX (ZnMP) and the effect of pH on their binding to liposomes have been studied. The ionization constants for the two carboxylate groups of ZnHP were calculated by principal component analysis and are 5.7 ± 0.1 and 6.9 ± 0.05. The neutral species and the mono- and dianionic forms all bind to liposomes, but a strong pH effect on the binding constant was observed for both the investigated compounds. We also observed a decrease in the binding of the two anionic species when the membranes carried a negative charge. These results indicate that the porphyrins partition into the membrane with their carboxylic moieties near the lipid–water interface so that their deprotonation, leading to a charged molecule, does not prevent the insertion of the tetrapyrrole ring into the lipid environment of neutral liposomes.