After being selected as part of the first group of astronauts to include women, Rhea Seddon flew on three Space Shuttle flights.

Her first space mission was as to conduct medical and scientific experiments including studying the behaviour of toys in a microgravity environment and the first ultrasound of a human heart. She also had to navigate a robot arm towards a satellite to activate its starter lever, something she was not prepared for but completed without a hitch. She logged 168 hours in space and orbited the earth 109 times.
Her second mission was on the first Spacelab Life Sciences Mission to discover the effects of near-zero gravity on the human body and to work out how quickly astronauts could recover. Her medical skills and as a mission specialist were vital for such experiments. She logged 218 further hours in space.
On the second Spacelab Life Sciences Mission, Rhea Seddon was the payload commander in charge of all science activities. For 14 days, the crew carried out medical experiments both on themselves and on 48 rats. NASA recognised it as the most efficient and successful Spacelab mission ever flown. It added 336 hours to Seddon’s space tally.