We compared the sequence polymorphism of 12 genomic fragments in six geographically dispersed African populations to one European Drosophila melanogaster population. On the basis of one African and one European population half of these fragments have strongly reduced levels of variability outside of Africa. Despite this striking difference in European variation, we detected no significant difference in African variation between the two fragment classes. The joint analysis of all African populations indicated that all high-frequency European alleles are of African origin. We observed a negative Tajima's D in all African populations, with three populations deviating significantly from neutral equilibrium. Low, but statistically significant, population differentiation was observed among the African populations. Our results imply that the population structure and demographic past of African D. melanogaster populations need to be considered for the inference of footprints of selection in non-African populations.