Related lines of Drosophila melanogaster selected for reproductive activity for more than 750 generations were studied. Results of the long-term selection experiment support D.K. Belyaev's concept of destabilizing selection. Selection for a behavioral trait (male mating activity) affected the intrinsic structure of the organism. Flies of the low-activity line (LA) exhibited numerous morphological, biochemical, and physiological alterations. Variation rate in the selected lines was accelerated; appearing mutations were often allelic and nonrandomly distributed over chromosomes. Selection was shown to mediate novel sources of variability, e.g., induction and repression of the hobo hybrid dysgenesis. In the process of selection, a genetically determined program of hobo transpositions in the genome was formed.