Abstract Duraisingh, M. T., Curtis, J., and Warhurst, D. C. 1998. Plasmodium falciparum:Detection of polymorphisms in the Dihydrofolate reductaseand dihydropteroate synthetasegenes by PCR and restriction digestion. Experimental Parasitology 89,1–8. With the spread of resistance to chloroquine, the combination of sulphadoxine and pyrimethamine is growing in importance for the treatment of infection with the malaria parasite Plasmodium falciparum. Mutations in the dhfrgene of P. falciparumhave been associated with resistance to pyrimethamine. Recently, several polymorphisms have been identified in the P. falciparum dhpsgene which may correlate with sulphadoxine-resistance. Simple and rapid tests have been developed to detect these polymorphisms, using PCR followed by restriction digestion. These tests can accurately identify all the polymorphisms described to date at codons 16, 51, 59, 108, and 164 in the dhfrgene and those at codons 436, 437, 540, 581, and 613 in the dhpsgene. A nested system has been developed which allows the accurate detection of these polymorphisms in samples of fingerprick blood collected on glass fiber membranes and filter papers, some with very low parasitaemias.