Cintineo, HP, Freidenreich, DJ, Blaine, CM, Cardaci, TD, Pellegrino, JK, and Arent, SM. Acute physiological responses to an intensity-and time under-under-tension-equated single- vs. multiple-set resistance training bout in trained men. J Strength Cond Res 32(12): 3310-3318, 2018-Regardless of the setting, proper manipulation of resistance training program design variables is pivotal in eliciting the desired physiological adaptations. Furthermore, how these variables, especially volume and intensity, work together to affect training outcomes is a major topic of investigation. The purpose of this study was to compare the acute biochemical, physiological, and hormonal responses of a single-set accentuated eccentric high-intensity training (HIT) protocol to a traditional 3-set protocol to better understand the acute effects of volume. Resistance-trained male college students (N = 19; age = 21.11 ± 2.5 years; height = 174.33 ± 6.83 cm; body mass = 76.72 ± 10.24 kg; %BF = 15.53 ± 6.35%) participated in this study and were randomly assigned to either the 1-set HIT protocol (HIT) or the 3-set traditional (3ST) protocol. Heart rate (HR), blood lactate, salivary testosterone, and salivary cortisol levels were measured before, during, and at multiple time points after the exercise bout. Results showed no differences in average HR or testosterone at any time point between the 2 groups. However, the 3ST group exhibited higher values of peak HR, blood lactate during exercise, and cortisol during and 30 minutes after exercise than the HIT group. This indicated that the 3ST protocol induced greater metabolic stress and disrupted the homeostatic balance to a greater magnitude than the HIT protocol despite similar time under tension. These results show that even when training to momentary muscular failure, volume seems to be a key driver of the training stimulus.