Aims. This study explored the process of arterial baroreflex adaptation to microgravity, starting from the first day of flight, during the 16-day STS-107 Shuttle mission. Methods. Continuous blood pressure (BP), ECG and respiratory frequency were collected in 4 astronauts on ground (baseline) and during flight at days 0-1, 6-7 and 12-13, both at rest and during moderate exercise (75W) on a cycle-ergometer. Sensitivity of the baroreflex heart rate control (BRS) was assessed by sequence and spectral alpha methods. Baroreflex effectiveness index (BEI), Low (LF) and high frequency (HF) powers of systolic (S) and diastolic (D)BP and RR interval (RRI), the RRI LF/HF ratio and the RRI Root Mean Square of Successive Differences (RMSSD) index were also estimated. Results. At rest, BRS increased in early flight phase, as compared with baseline (mean+/-SE: 18.3+/-3.4 vs.10.4+/-1.2 ms/mmHg, p<0.05), and tended to return to baseline in subsequent days. During exercise, BRS was lower than at rest, without differences between pre-flight and in-flight values. At rest, in the early flight phase, RMSSD and RRI HF power increased (p<0.05) as compared with baseline, while LF powers of SBP and DBP decreased. No statistical difference was found in these parameters during exercise before vs. during flight. Conclusions. Heart rate baroreflex sensitivity and markers of cardiac vagal modulation are enhanced during early exposure to microgravity, likely because of the blood centralization, and return to baseline values in subsequent flight phases, possibly because of the fluid loss. No deconditioning seems to occur in the baroreflex control of the heart.