The role of oxidant stress in mediating the protection against malaria in thalassaemic red blood cells (RBC) has been hypothesized. In this study we have assessed the relationship between oxidant stress, red cell age and malarial parasite activity in thalassaemic RBC. Using a flow cytometric method to assess lipid peroxidation, we have shown that the age-related increase in sensitivity to oxidative stress previously demonstrated in normal RBC also occurs in thalassaemic RBC. Invasion and growth of Plasmodium falciparum was also shown to deteriorate with increasing RBC age. This effect was more pronounced in thalassaemic RBC with associated schizont maturation arrest and abnormal parasite morphology. In addition, there was a slight but consistent inverse correlation between sensitivity to oxidant stress and parasite activity (R=−0·43; P=0·03 for normal RBC and R=−0·42; P=0·01 for thalassaemic RBC). Our findings indicate an association between red cell age, oxidant stress and P. falciparum growth, providing further support for the role of oxidant stress in mediating the protective effect against malaria in thalassaemic RBC.