We correlated the fatigue resistance (FR) of the costal diaphragm (DIA) and external abdominal oblique (EAO) of the rat during postnatal development with their respective 1) myosin heavy chain (MHC) phenotypes and 2) oxidative capacities [indexed by quantitative measurements of succinic dehydrogenase (SDH) enzyme activity]. FR was measured in vitro during isometric contractions with the use of the Burke fatigue test. FR of the DIA and EAO was high in newborns and declined during postnatal development. SDH activity was uniformly low in neonatal DIA and EAO and increased during early postnatal development before declining to adult levels. FR did not significantly correlate with SDH activity (r2 = 0.01) but did relate to the MHC phenotype as indexed by the ratio of adult MHC isoform content (slow + IIa + IIx + IIb) to developmental MHC isoform content (slow + neonatal; r2 = 0.88, P < 0.01). Stepwise regression revealed that neonatal MHC expression alone accounted for 60% of the developmental variance in FR. The correlation between FR and MHC phenotype was improved if SDH was also considered, i.e., the ratio of SDH to MHC phenotype (r2 = 0.99, P < 0.01). We conclude that FR of respiratory muscle during development relates to a balance between the energetic demands of the muscle contractile proteins as reflected by MHC isoform composition and its oxidative capacity with MHC phenotype alone exerting a strong predictive effect on FR.