Masumoto, K, Mefferd, KC, Iyo, R, and Mercer, JA. Muscle activity and physiological responses during running in water and on dry land at submaximal and maximal efforts. J Strength Cond Res 32(7): 1960–1967, 2018—We investigated muscle activity, oxygen uptake, heart rate, and rating of perceived exertion during running in water and on dry land at submaximal and maximal efforts. Eleven recreational runners performed deep-water running (DWR) and treadmill running (TMR) graded exercise tests on separate days. On the third-test day, the subjects exercised at their 60, 80, and 100% of maximal oxygen uptake (V[Combining Dot Above]O2max) by matching specific stride frequencies or running speeds. V[Combining Dot Above]O2max, maximal heart rate (HRmax), and rating of perceived exertion at maximal effort (RPEmax) were measured. Furthermore, muscle activity from the rectus femoris, biceps femoris, tibialis anterior, and gastrocnemius were measured. V[Combining Dot Above]O2max (DWR: 48.9 ± 5.7 ml·kg−1·min−1; TMR: 59.2 ± 5.6 ml·kg−1·min−1; p < 0.001) and HRmax (DWR: 174.1 ± 9.6 beats·min−1; TMR: 191.2 ± 6.9 beats·min−1; p < 0.001) were each lower during DWR vs. TMR. In addition, RPEmax was not significantly different between DWR and TMR (DWR: 17.8 ± 1.9; TMR: 18.4 ± 1.3; p > 0.05). Furthermore, muscle activity from all tested muscles was not influenced by the interaction of mode and intensity (p > 0.05). Muscle activity from all tested muscles was different between modes (p < 0.05) and between intensities (p < 0.001). Specifically, muscle activity from the tested muscles during DWR was 29–69% lower than that of TMR at maximal effort. Athletes and coaches should consider that the exercise intensity during DWR can be overestimated, if exercise prescription was made according to the maximal responses during TMR.