Mangine, GT, Hoffman, JR, Gonzalez, AM, Townsend, JR, Wells, AJ, Jajtner, AR, Beyer, KS, Boone, CH, Wang, R, Miramonti, AA, LaMonica, MB, Fukuda, DH, Witta, EL, Ratamess, NA, and Stout, JR. Exercise-induced hormone elevations are related to muscle growth. J Strength Cond Res 31(1): 45-53, 2017-Partial least squares regression structural equation modeling (PLS-SEM) was used to examine relationships between the endocrine response to resistance exercise and muscle hypertrophy in resistance-trained men. Pretesting (PRE) measures of muscle size (thickness and cross-sectional area) of the vastus lateralis and rectus femoris were collected in 26 resistance-trained men. Participants were randomly selected to complete a high-volume (VOL, n = 13, 10-12RM, 1-minute rest) or high-intensity (INT, n = 13, 3-5RM, 3-minute rest) resistance training program. Blood samples were collected at baseline, immediately postexercise, 30-minute, and 60-minute postexercise during weeks 1 (week 1) and 8 (week 8) of training. The hormonal responses (testosterone, growth hormone [22 kD], insulin-like growth factor-1, cortisol, and insulin) to each training session were evaluated using area-under-the-curve (AUC) analyses. Relationships between muscle size (PRE), AUC values (week 1 + week 8) for each hormone, and muscle size (POST) were assessed using a consistent PLS-SEM algorithm and tested for statistical significance (p ≤ 0.05) using a 1,000 samples consistent bootstrapping analysis. Group-wise comparisons for each relationship were assessed through independent t-tests. The model explained 73.4% (p < 0.001) of variance in muscle size at POST. Significant pathways between testosterone and muscle size at PRE (p = 0.043) and muscle size at POST (p = 0.032) were observed. The ability to explain muscle size at POST improved when the model was analyzed by group (INT: R = 0.882; VOL: R = 0.987; p < 0.001). No group differences in modal quality were found. Exercise-induced testosterone elevations, independent of the training programs used in this study, seem to be related to muscle growth.