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Kudrna, RA, Fry, AC, Nicoll, JX, Gallagher, PM, and Prewitt, MR. Effect of three different maximal concentric velocity squat protocols on MAPK phosphorylation and endocrine responses. J Strength Cond Res 33(6): 1693–1703, 2019—The purpose of this study was to determine the effect of 3 different back squat protocols on intracellular signaling, endocrine responses, and power fatigue. Nine recreationally trained men (X ± SD; age: 21.4 ± 0.6 years; height: 177.8 ± 5.1 cm; body mass: 78.7 ± 9.7 kg), completed 3 maximal concentric velocity squat protocols in a randomized order. Testing protocols consisted of 5 sets of 10 repetitions at 30% of 1 repetition maximum (1RM); 5 sets of 5 repetitions at 70% of 1RM; and 5 sets of 3 repetitions at 90% of 1RM. Average system power for each set was obtained using a tethered external dynamometer. Pre-exercise and postexercise blood draws were analyzed for lactate, testosterone, human growth hormone (hGH), and cortisol. Muscle biopsies assessed pre-exercise and postexercise extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 phosphorylation using western blotting. Cortisol, hGH, and lactate increased after exercise (p ≤ 0.05), but did not differ between protocols (p > 0.05). Testosterone was unaltered (p > 0.05). Average power was lower for the 90% protocol than for the 30% protocol across all sets (p < 0.01). Average power was lower after the fourth and fifth set compared with the first and second set in the 90% protocol only (p ≤ 0.05). The ratio of phosphorylated-to-total ERK1/2 was higher postexercise after 90% protocol only (p ≤ 0.05). The ratio of phosphorylated-to-total p38 was unaltered after exercise (p > 0.05). Resistance load seems to affect power fatigue across the 5 sets of resistance exercise. This study found modest changes in ERK1/2 and no changes in p38 phosphorylation after maximal concentric velocity squats. Exercise volume, modality, and training status of subjects may account for these findings.