During exercise below the lactate threshold (LT), the rate of adjustment (τ) of pulmonary VO(2) uptake (τ) is slowed when initiated from a raised work rate. Whether this is consequent to the intrinsic properties of newly recruited muscle fibres, slowed circulatory dynamics or the effects of a raised metabolism is not clear. We aimed to determine the influence of these factors on τV(O(2)) using combined in vivo and in silico approaches. Fifteen healthy men performed repeated 6 min bouts on a cycle ergometer with work rates residing between 20 W and 90% LT, consisting of the following: (1) two step increments in work rate (S1 and S2), one followed immediately by the other, equally bisecting 20 W to 90% LT; (2) two 20 W to 90% LT bouts separated by 30 s at 20 W to raise muscle oxygenation and pretransition metabolism (R1 and R2); and (3) two 20 W to 90% LT bouts separated by 12 min at 20 W allowing full recovery (F1 and F2). Pulmonary O(2) uptake was measured breath by breath by mass spectrometry and turbinometry, and quadriceps oxygenation using near-infrared spectroscopy. The influence of circulatory dynamics on the coupling of muscle and τV(O(2)) lung was assessed by computer simulations. The τV(O(2)) in R2 (32 ± 9 s) was not different (P > 0.05) from S2 (30 ± 10 s), but both were greater (P < 0.05) than S1 (20 ± 10 s) and the F control bouts (26 ± 10 s). The slowed V(O(2)) kinetics in R2 occurred despite muscle oxygenation being raised throughout, and could not be explained by slowed circulatory dynamics (τV(O(2)) predicted by simulations: S1 = R2 < S2). These data therefore suggest that the dynamics of muscle O(2) consumption are slowed when exercise is initiated from a less favourable energetic state.