INTRODUCTION: Few studies have attempted to investigate the influence of prolonged head-down bed rest (HDBR) on hypercapnic ventilatory chemosensitivity, and there are no data available regarding associated changes in arterial BP and heart rate (HR). The aim of this study was to clarify the influence of prolonged HDBR on ventilatory and cardiovascular responses to hypercapnia. METHODS: There were five healthy men who participated in this study. Resting ventilatory and cardiovascular responses to hypercapnia were measured by means of Read's CO2 rebreathing method 4 d before and on the 19th day of HDBR. Measured variables included systolic and diastolic BP (SBP and DBP, respectively), inspired minute ventilation (VI), and end-tidal partial pressure of CO2 (PETCO2). RESULTS: Ventilatory response to hyperoxic hypercapnia (deltaVI/ deltaPETCO2) decreased significantly on the 19th day of HDBR (1.42 +/- 0.65 to 0.90 +/- 0.41 L x min(-1) x torr(-1), p < 0.05). On the other hand, SBP, DBP, and HR responses (deltaSBP/deltaPETCO2, deltaDBP/deltaPETCO2, and deltaHR/deltaPETCO2) were unchanged. DISCUSSION: The results from this study suggest that prolonged HDBR leads to diminished central hypercapnic ventilatory chemosensitivity.