We show that two complementary asymmetric isolating mechanisms, likely mediated by divergence in body size, underlie the evolution of incipient reproductive isolation between a set of Drosophila melanogaster populations selected for rapid development and their ancestral controls. Selection has led to great reduction in body size in the fast developing lines. Small males belonging to fast developing lines obtain few matings with large control females, both in presence and absence of large control line males, giving rise to unidirectional, premating isolation caused by sexual selection. Conversely, small selected line females suffer greatly increased mortality following mating with large control males, causing unidirectional postcopulatory prezygotic isolation. We discuss preliminary evidence for evolution of reduced male harm caused to females upon mating in the fast developing lines, and speculate that the females from these lines have coevolved reduced resistance to male harm such that they can no longer resist the harm caused by males from control lines. This potentially implicates differing levels of sexual conflict in creating reproductive barrier between the selected line females and the control males. We also show that a large difference in development time is not sufficient to cause postzygotic incompatibilities in the two sets of populations reaffirming the belief that prezygotic isolation can evolve much earlier than postzygotic isolation.