Preflight, inflight, and postflight exercise response tests were conducted on the astronauts of the second Skylab mission (Skylab 3) as part of an evaluation of physiological adaptation to long-term weightlessness. The flight phase of this mission was 59 d in duration. An exercise protocol was designed around a bicycle ergometer which was used to apply work loads approximating 25, 50, and 75% of each crewman's measured maximum aerobic capacity (VO2 max). Respiratory gas exchange (VO2, VCO2, and VE), heart rate, and blood pressure were measured during all tests; cardiac output was measured at selected times during preflight and postflight tests. Data obtained both at rest and during exercise in flight showed no consistent changes which would indicate a degraded physical work capacity. In fact, heart rate during exercise actually decreased for all crewmen in flight. This response indicated improved physical fitness in flight relative to preflight. The improved physical condition of this crew relative to that of the first Skylab crew is attributed to frequent performance of high levels of aerobic exercise in flight. The postflight period of readaptation of 1 G was characterized by a marked tachycardia, during which time stroke volume was decreased. This response returned to normal within 5 d postflight.