We attempted to analyze how PACO2 is regulated during progesterone-induced hyperventilation in the luteal phase. A model for the CO2 control loop was constructed, in which the function of the CO2 exchange system was described as PACO2 = 0.863 x VCO2/VA (gain H = dPACO2/dVA) and that of the CO2 sensing system as VA = S (PACO2 - B). Using this model, we estimated (1) the primary increase in VA (delta VA (op)) produced by progesterone stimulation and (2) the effectiveness (E) of the loop to regulate PACO2, defined as delta PACO2 (op)/delta PACO2 (cl) in which op signifies open-loop and cl, closed-loop. These respiratory variables were investigated throughout the menstrual cycle in 8 healthy women. During the luteal phase, on average, VA increased by 9.4% and PACO2, B and H decreased by 0.33 kPa (2.5 mm Hg), 0.47 kPa (3.5 mm Hg) and 13.6%, respectively, while S and VCO2 did not change significantly. Delta VA (op) increased progressively on successive days of the luteal phase while E remained unchanged at a value of 7.9, thus there was a progressive decrease in PACO2. The decrease in H was considered to lessen delta PACO2 (op) and so reduce the final deviation of PACO2 (delta PACO2 (cl) during the luteal phase. The decrease in B was found to be dependent on delta VA (op).