Oesophageal striated muscle of several mammalian species receives dual innervation from both vagal motor fibres originating in the brain stem and enteric nerve fibres originating in myenteric ganglia. The aim of this study was to investigate this so-called enteric co-innervation in the human oesophagus. Histochemical and immunohistochemical methods combined with confocal laser scanning microscopy were utilized to study innervation of 14 oesophagi obtained from body donors (age range 47-95 years). In addition, the distribution of striated and smooth muscle in longitudinal and circular layers of the tunica muscularis was studied semiquantitatively. The upper half of the oesophagus was built up of both muscle types with a predominance (>50-60%) of striated muscle, whereas the lower half consisted of smooth muscle only. The majority of motor endplates was compact and ovoid. Enteric nerve fibres on approximately 17% of motor endplates stained for neuronal nitric oxide synthase, vasoactive intestinal polypeptide, galanin and neuropeptide Y and were completely separated from vagal cholinergic nerve terminals. There was remarkable variability of co-innervation rates between striated muscle bundles with some reaching almost 50%. Myenteric neurons representing the putative source of enteric co-innervating nerve fibres, stained for all these markers, which were almost completely colocalized with NADPH-diaphorase. Our study provides evidence for enteric co-innervation of striated muscle in human oesophagus. From these and recent functional results in various rodent species, we suggest that this innervation component represents an integral part of an intramural reflex mechanism for local most likely inhibitory modulation of oesophageal motility.