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Insect-reared Anopheles gambiae were experimentally fed with the blood of naturally infected human volunteers carrying gametocytes of Plasmodium falciparum. Infection of at least one mosquito was successful in 86 experiments. For these gametocyte carriers, the hemoglobin types studied were AA (normal, n = 77), AS (heterozygous sickle cell, n = 8), and SS (homozygous sickle cell, n = 1). The mean of the percentages of infected mosquitoes by gametocyte carriers of AS hemoglobin was almost double that of carriers of AA: 30.4% versus 17.5%. The genetic protection in humans conferred by the βs gene in its heterozygous form seems to be associated with an increasing effect on P. falciparum transmission from humans to mosquitoes. The epidemiologic and evolutionary aspects of this finding are discussed.