In order to understand how divergence may appear within a gene pool without limitations on gene flow, experiments were performed to investigate whether the genetic structure of a population may be effective in controlling the response to natural selection. Starting from plateaued populations of Drosophila melanogaster selected for wing length on the two sexes separately, the response to natural selection was studied after artificial selection had been discontinued. The results show that populations derived from artificial selection applied to the different sexes respond to subsequent natural selection in dissimilar ways, so as to suggest that the relationships between fitness and wing length have been changed. A second experiment comparing the response to natural and to artificial reversed selection suggests that different genes or gene complexes may be involved in wing length determination: these different genes show a dissimilar response in the different sexes and to natural and artificial selection. This variety of responses suggests that the interactions of different genes or gene complexes with artificial and natural selection could possibly lead to differentiation within the population.