We report a patient presenting with severe muscular impairment and chronic intestinal pseudo-obstruction (CIP) at the age of eight months. Due to the aggravated symptoms, assisted ventilation, an ileostomy and total parenteral nutrition were required. Later on, the patient developed a locked-in syndrome (Leigh's subacute necrotising encephalomyelopathy) and finally died due to recurrent pneumonia and chronic renal failure. The assessment of muscle biopsies revealed a moderate single-fibre type II atrophy, a variation of muscle fibre calibre with focal fatty degeneration and a decreased reactivity of cytochrome-c oxidase. Although ragged red fibres had not been found, mitochondrial enzyme activities were markedly decreased with the lowest residual activity detected for NADH:Q1 oxidoreductase and NADH:O2 oxidoreductase (complex I deficiency), thereby confirming the diagnosis of mitochondrial myopathy. A molecular genetic analysis could not identify known mutations of mitochondrial DNA. Gastrointestinal full-thickness biopsies revealed myenteric hypoganglionosis of the colon and stomach and hyperplasia of the submucosal plexus of the ileum. Some of the intestinal smooth muscle cells displayed bulbous protrusions filled with lateralised mitochondria. Mitochondrial myopathies are known to be associated with a variety of clinical syndromes including CIP. However, in contrast to previous reports in which CIP has been attributed to visceral intestinal myopathies, the present case is characterised by neuronal intestinal malformations. Therefore, a mitochondrial myopathy associated with CIP requires a subtle assessment of both the intestinal smooth muscle and the enteric nervous system to identify the underlying pathology.