The hematologic and immunologic functions of the Skylab 3 (second manned mission) astronauts were examined during the preflight, inflight, and postflight phases of the 59-d mission in order to evaluate the response to and/or the influence of the space flight environment. Most changes observed were subtle and did not represent a threat to the health and safety of the crewmen during orbital flight. Even the most significant change observed, a reduction in the circulating red cell mass, did not have a detrimental influence on the astronaut cardiovascular or exercise responses as evaluated by other experiment protocols. Considering the facts that the data were not collected under ideally controlled conditions and that the astronauts were in excellent physical condition, the results of these studies would seem to indicate that man can function quite well in the space flight environment of the Skylab orbiting workshop for extended periods of time.