In this paper we discuss results from a recent high fidelity simulation of air traffic control operations with automated separation assurance in the presence of weather and time-constraints. We report findings from a human-in-the-loop study conducted in the Airspace Operations Laboratory (AOL) at the NASA Ames Research Center. During four afternoons in early 2010, fifteen active and recently retired air traffic controllers and supervisors controlled high levels of traffic in a highly automated environment during three-hour long scenarios, For each scenario, twelve air traffic controllers operated eight sector positions in two air traffic control areas and were supervised by three front line managers, Controllers worked one-hour shifts, were relieved by other controllers, took a 3D-minute break, and worked another one-hour shift. On average, twice today's traffic density was simulated with more than 2200 aircraft per traffic scenario. The scenarios were designed to create peaks and valleys in traffic density, growing and decaying convective weather areas, and expose controllers to heavy and light metering conditions. This design enabled an initial look at a broad spectrum of workload, challenge, boredom, and fatigue in an otherwise uncharted territory of future operations. In this paper we report human/system integration aspects, safety and efficiency results as well as airspace throughput, workload, and operational acceptability. We conclude that, with further refinements. air traffic control operations with ground-based automated separation assurance can be an effective and acceptable means to routinely provide very high traffic throughput in the en route airspace.