This report discusses the basic biotechnology research problems that require solution by the year 2000 to ensure optimum performance of manned Air Force aeronautical systems. The projected aeronautical systems for strategic, tactical and support systems are discussed, with emphasis placed on the roles of increased automation and information processing, as well as the increased physical stress of higher performance aircraft, extended mission durations and new weapon threats. Six generic areas of biotechnology are considered, along with the research needed to address the needs of the year 2000 aircrew. First discussed is the human-machine symbiosis needed in systems that will become extraordinarily complex. This is followed by the related needs in developing improved human-machine information interfaces that avoid overloading the human operator or pilot. Many missions of the future will be unforgiving and of high intensity. The problems and research needed to deal with the increased stress and to protect and enhance aircrews' performance during these missions are discussed in detail. The report discusses how simulators can be advanced to provide not only better training for aircrews, but also how they can be used in the development of new systems for optimizing the human-information-machine relationship.