A letter from Drs. G. I. Robertson, D. G. Davey, and Sir Hamilton Fairley (December 6, 1952, p. 1255) reported that a proguanil-resistant strain of Plasmodium falciparum from Malaya had proved to be resistant also to pyrimethamine (" daraprim "). Proguanil-resistance in Malayan strains of P. falciparum has been recognized since 19491; and if a true cross-resistance exists, this might-as implied by Dr. J. S. K. Boyd (February 7, p. 337)-go far to explain the pyrimethamine failures described in our paper (January 31, p. 253). Proguanil has been so widely used throughout Malaya for the past six years that there can be few strains of parasite which have not yet come into contact with it; thus there is little chance of deciding now how the "parent" strains (without previous contact with proguanil) might have responded to pyrimethamine. We have not, however, been able to confirm that there is any consistent cross-resistance between these two drugs in naturally acquired falciparum malaria since pyrimethamine was first used in Malaya in 1951. Pyrimethamine failures have been successfully treated with normal doses of proguanil, and proguanilresistant infections have responded readily to pyrimethamine. In some of these cases an interval of several days was allowed to elapse between treatments, so the possibility of a combined action of the two drugs should have 'been small. We consider that these apparently conflicting results can best be explained by assuming that some present-day strains of P. falciparum in Malaya possess a " natural" resistance to pyrimethamine, whether or not any particular strain is also demonstrably resistant to proguanil. With this species of parasite, a true cross-resistance has still to be proved. REFERENCE 1 British Medical Journal, 1950. 1, 147.