Space motion sickness is a well-recognized problem for space flight and affects 73% of crewmembers on the first 2 or 3 days of their initial flight. Illness severity is variable, but over half of cases are categorized as moderate to severe. Management has included elimination of provocative activities and delay of critical performance-related procedures such as extra-vehicular activity (EVA) or Shuttle landing during the first three days of missions. Pharmacological treatment strategies have had variable results, but intramuscular promethazine has been the most effective to date with a 90% initial response rate and important reduction in residual symptoms the next flight day. Oral prophylactic treatment of crewmembers with difficulty on prior flights has had mixed results. In order to accommodate more aggressive pharmacologic management, crew medical officers receive additional training in parenteral administration of medications. Preflight medication testing is accomplished to reduce the risk of unexpected performance decrements or idiosyncratic reactions. When possible, treatment is offered in the presleep period to mask potential treatment-related drowsiness. Another phenomenon noted by crewmembers and physicians as flights have lengthened is readaptation difficulty or motion sickness on return to Earth. These problems have included nausea, vomiting, and difficulty with locomotion or coordination upon early exposure to gravity. Since landing and egress are principal concerns during this portion of the flight, these deficits are of operational concern. Postflight therapy has been directed at nausea and vomiting, and meclizine and promethazine are the principal agents used. There has been no official attempt at prophylactic treatment prior to entry. Since there is considerable individual variation in postflight deficit and since adaptation from prior flights seems to persist, it has been recommended that commanders with prior shuttle landing experience be named to flights of extended duration.