PURPOSE: Detrusor hyperreflexia is a common finding in patients with neurological disease involving the spinal cord. In animal models it has been attributed to an emergent reflex mediated mostly by unmyelinated C-fibers. We describe and measure ultrastructural features of these nerves in the lamina propria in healthy subjects and patients with detrusor hyperreflexia. MATERIALS AND METHODS: Flexible cystoscopic bladder biopsies were obtained from 51 patients (8 controls, 8 with tropical spastic paraparesis, 23 with multiple sclerosis and 12 with spinal cord disease). Electron micrographs were obtained of every nerve profile seen in the midpoint of the biopsy specimen, and in each nerve profile a number of variables were measured and recorded. RESULTS: The mean nerve profile diameter was greater in patients with tropical spastic paraparesis (mean 2.19 microm.) compared to controls (1.59 microm.) and patients with multiple sclerosis (1.55 microm.) (p <0.001). We observed a sparse urothelial innervation by naked axonal varicosities but similar bare varicosities were more frequent in the superficial layer of the lamina propria. In deeper layers close membrane contacts between axonal varicosities and cells with cytological characteristics of myofibroblasts were seen. CONCLUSIONS: We described and measured ultrastructural characteristics of human bladder lamina propria nerves. The mean profile diameter is larger in patients with tropical spastic paraparesis compared to controls and patients with multiple sclerosis. This study provides a baseline to which other bladder disorders can be compared and may allow the effect of intravesical treatments on these nerves to be assessed. Some possible functional aspects of observed structural interrelationships are presented.