Certain forms of Anopheles gambiae s.s. actively maintain malaria transmission in the driest areas and months of the year because of considerable drought tolerance. We monitored desiccation resistance of F1 offspring of both the M and S forms of field-collected An. gambiae s.s. Our results indicate that the geographic cline in the distribution of the two forms, as observed in Mali, corresponds to a physiological difference in response to arid environments. In addition, female mosquitoes survived significantly longer than males, enhancing the vector competence for the malaria parasite. Our study supports a genetic link to the drought tolerance phenotype, a phenotype with important consequences to malaria transmission in many places in Africa.