During ATP hydrolysis by Ca2+-activated chemically skinned fibers from the flight muscle of the giant waterbug Lethocerus indicus, there is extensive phosphate-water oxygen exchange. For unstrained fibers the pattern of exchange shows that there is more than one pathway for hydrolysis, due to the ATPase activity of cross-bridges. Multiple pathways are an established property of both vertebrate actomyosin and fibers. The pattern of exchange can be fitted by two pathways: one with low exchange because the step(s) controlling Pi release are rapid, the other with high exchange and slow Pi release. The high-exchange pathway is responsible for most of the increase in ATPase activity on Ca2+ activation. On strain activation, only the high-exchange pathway is present, accounting for all the ATPase increase and responsible for force generation. In fully activated fibers, the cross-bridges which hydrolyze ATP and generate force behave uniformly with respect to oxygen exchange. The exchange pattern shows that the rate of Pi release changes dramatically over a very narrow strain increase. Step(s) controlling Pi release are at least partially rate-limiting for the overall ATPase reaction. The results are discussed in relation to models for strain activation and the identity of force-generating states.