Although the advantages of flight at high altitude were early recognized, so also were the physiological problems standing in the way of its realization. The idea of surmounting such problems by means of a pressurized cabin was advocated as early as 1909, while the first attempt to translate the concept into actuality occurred in 1921. Neither it nor several successive attempts enjoyed any real success until a project launched by the U. S. Air Corps in 1935 produced a breakthrough aircraft (...) designated the XC-35. The major reason for the favorable termination of that venture was the thoroughness of the engineering involved. But it is equally notable that this was the first instance in the age of powered flight where there was an active collaboration between the scientists and engineers, a rather curious circumstance in view of the fact that the achievement of altitude record-setting balloon flights in the nineteenth century had owed a great deal to an interconnection of aeronauts and scientists' laboratories. This paper focuses on the physiological investigations which informed the XC-35 engineers while at the same time bringing into being a new aeromedical laboratory taking the first small step toward turning aeromedicine into space medicine. (shrink)