Previous studies have shown that amine groups are ototoxic. The interaction between different polyamines and phospholipid vesicles was studied using vesicle aggregation and fluorescence techniques (DPH and ANS as the fluorescence probes). The results showed that the interaction between polyamines (spermine, spermidine and 1,3-diaminopropane) and acidic phospholipids (PS, PE, PI and PIP2) is an ionic one. The polyamine with the highest positive charges and the phospholipid with the highest content of negative groups showed the strongest ionic interaction. There was no indication of any hydrophobic interaction within the phospholipid bilayer. The strong interaction between amine groups and PIP2 support the proposal that the latter is crucially involved in aminoglycoside toxicity in the inner ear and kidney.