Duchenne muscular dystrophy (DMD) is a neuromuscular disorder resulting in impaired skeletal muscle force-generating capacity, with attendant muscle fibre remodelling. Dystrophin deficiency leads to reduced respiratory muscle strength and premature death due to cardiorespiratory failure. DMD has been extensively researched in animal models such as the dystrophin-deficient mdx mouse. Alterations to the specialised structure of the neuromuscular junction have been described in mdx mice, which may lead to adaptive or mal-adaptive changes in neuromuscular communication. It is unclear if altered neuromuscular transmission contributes to impaired respiratory muscle performance in DMD and mdx mice and how this might change over the course of disease progression. We examined the effects of dystrophin deficiency on diaphragm neuromuscular transmission and diaphragm muscle function ex vivo in male wild-type and mdx mice.   We assessed diaphragm neuromuscular transmission in wild-type (n=12) and mdx (n=12) mice at 4- and 8-months of age using an ex vivo nerve-muscle preparation (phrenic-diaphragm). Phrenic-diaphragm preparations were studied in Krebs solution bubbled with 95% O2/ 5% CO2 at 35oC. The phrenic nerve was stimulated via a glass suction electrode while the diaphragm muscle was stimulated directly via field stimulation using platinum electrodes. Phrenic-diaphragm preparations were stimulated at 25, 50, 75 and 150Hz to establish force-frequency relationships. Next, neuromuscular transmission for phrenic-diaphragm preparations was examined by repeatedly stimulating the phrenic nerve every 2s and the diaphragm muscle every 15s at 50Hz. Neuromuscular transmission failure was calculated by comparative differences in nerve- and muscle-evoked force. Data were statistically compared using two-way ANOVA with Bonferroni post hoc test. P<0.05 was considered statistically significant.   Diaphragm specific force was depressed for mdx preparations compared to age-matched wild-type at high stimulation frequencies (75-150 Hz). Diaphragm specific force was equivalent in response to nerve and muscle stimulation for both wild-type and mdx preparations at both ages, but specific force for mdx preparations remained lower compared to wild-type. Repeated stimulation at 50Hz resulted in significant neuromuscular transmission failure for wild-type phrenic-diaphragm preparations, whereas neurotransmission for mdx preparations was remarkably preserved at 4- and 8-months of age.   These data demonstrate profound muscle weakness in dystrophin-deficient diaphragm. Neuromuscular transmission data suggests compensatory plasticity is present in mdx diaphragm, allowing dystrophic diaphragm to preserve neuromuscular transmission during repeated stimulation at 50Hz albeit in the context of significant muscle weakness. A greater appreciation of neuromuscular communication in dystrophin-deficient diaphragm is essential to understand the neuro-mechanical control of breathing in muscular dystrophy. Examining compensatory mechanisms that act to preserve neuromuscular transmission in DMD may lead to the identification of potential therapeutic targets.