The safety of astronauts in habitats beyond Earth has always represented a challenge to the disciplines of environmental health and occupational medicine. The forthcoming long duration missions present new challenges in space environmental health. The space habitat is similar to a small tight building. Both chemical and microbial contaminants have the potential to accumulate in an atmosphere of limited volume and turnover. Microgravity and the absence of convection currents will produce unusual behavior of suspended particles and of fluid and mass transport in the habitat and life systems.The response of astronauts to both toxic chemicals and infective biota may differ from the Earth-based situation. Their physiological status is altered in not totally understood ways in microgravity, and there is the potential of additional stress from solar and cosmic radiation. They will be exposed to a diverse range, concentration and type of potential contaminants. Exposures will consist of chronic to low levels and possibly acute to high levels in the case of accidents. The health effects of concern are those that will affect the performance of the astronauts in such a way as to endanger their safety or the performance of the mission.