Various regulatory mechanisms of pulmonary oxygen uptake ((V)over dotO(2)) kinetics have been postulated. The purpose of this study was to investigate the relationship between vagal withdrawal, measured using RMSSDRR, the root mean square of successive differences in cardiac interval (RR) kinetics, a mediator of oxygen delivery, and (V)over dotO(2) kinetics. Forty-nine healthy adults (23 +/- 3 years; 72 +/- 13 kg; 1.80 +/- 0.08 m) performed multiple repeat transitions to moderate-and heavy-intensity exercise. Electrocardiography, impedance cardiography, and pulmonary gas exchange parameters were measured throughout; time domain measures of heart rate variability were subsequently derived. The parameters describing the dynamic response of tau (V)over dotO(2), cardiac output (tau Q) and RMSSDRR were determined using a mono-exponential model. During heavy-intensity exercise, the phase II t of (V)over dotO(2) was significantly correlated with the t of RR (r = 0.36, P < 0.05), Q (r = 0.67, P < 0.05), and RMSSDRR (r = 0.38, P < 0.05). The t describing the rise in Q explained 47% of the variation in (V)over dotO(2) tau, with 30% of the rate of this rise in Q explained by the t of RR and RMSSDRR. No relationship was evident between (V)over dotO(2) kinetics and those of Q, RR, or RMSSDRR during moderate exercise. Vagal withdrawal kinetics support the concept of a centrally mediated oxygen delivery limitation partly regulating (V)over dotO(2) kinetics during heavy-, but not moderate-, intensity exercise.