Polyoxyethylene alkyl ether surfactants have been shown to have excellent penetration enhancing abilities although they are associated with a high level of local toxicity. We have compared the toxicity of a range of polyoxyethylene alkyl ethers (Brij 96, Brij 76, Brij 56, 10 lauryl ether and 9 lauryl ether) to an anionic surfactant (sodium dodecyl sulphate (SDS)), an ampholytic surfactant (lysophosphatidylcholine) and a cationic surfactant (tetradecyltrimethylammonium bromide (TTAB)), in the presence and absence of egg phosphatidylcholine. The toxicity of the surfactants or phospholipid/surfactant mixtures was assessed by measuring haemolytic activity. The test samples were incubated with a suspension of red blood cells for 30 min and Drabkin's reagent was used to indicate the amount of haemoglobin released. All of the polyoxyethylene alkyl ethers, SDS, TTAB and lysophosphatidylcholine exhibited haemolytic activity at concentrations between 0.10 and 0.25 mM. The addition of egg phosphatidylcholine reduced the toxicity for all of the surfactants, with the toxicity of Brij 96 being mitigated to a greater extent than the toxicity of the other polyoxyethylene surfactants examined. The rate of haemolysis induced by Brij 96 or 10 lauryl ether was also reduced by increasing concentrations of phosphatidylcholine. As the phosphatidylcholine content of a mixed surfactant system comprising egg phosphatidylcholine: Brij 96 was replaced by lysophosphatidylcholine and fatty acid, the haemolytic action of the mixture increased markedly. The results from this study show that the toxicity of surfactants to erythrocytes can be mitigated by the addition of egg phosphatidylcholine. Synthetic surfactants combined with phosphatidylcholine may generate drug delivery systems worthy of more extensive investigation.