Certain human genetic variants occur on-ly in areas endemic for malaria. They protect against fatal malaria complications and cause inhibition of growth or development of malaria parasites in vitro. Among these are the haemoglobins (Hb) S and C, alpha-thalassaemias, glucose-6-phosphate dehydrogenase deficiency, as well as a deletion in the erythrocyte band 3 protein. Evidence for similar effects has been obtained for HbD and HbE, glycophorins A and C as well as for a number of immunologically relevant molecules such as human leukocyte antigens,tumour-necrosis-factor a and the inducible nitric oxide synthase. The findings indicate that malaria in endemic areas has caused a substantial selection of the human genome.