PURPOSE The present study aims to examine the effect of complete outlet obstruction on the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reactivity in the intramural ganglion cells of the guinea pig urinary bladder. MATERIALS AND METHODS Adult male guinea pigs were divided into control (normal and sham-operated) and urethral obstructed (12, 24, and 48 hours after complete obstruction) groups. NADPH-d reactivity in the intramural neurons of the urinary bladder was examined by light and electron microscopy. RESULTS At 12 hours after urethral obstruction, an increase in number of intensely stained NADPH-d intramural neurons was detected. This was sustained till 24 hours whence some of the neurons appeared to undergo degenerative changes. Neuronal degeneration was more drastic at 48 hours. Results of cell counts showed a 32% reduction in number of NADPH-d positive neurons of the urinary bladder at this time point. Electron microscopy showed that all neurons undergoing degeneration displayed NADPH-d reactivity. A large accumulation of NADPH-d reaction product was observed in degenerating neurons whose mitochondria appeared swollen along with dilatation of Golgi saccules. At 48 hours, some neurons displayed total vacuolation and lysis of mitochondria. CONCLUSION Present results show that acute complete outlet obstruction can lead to degeneration and consequent cell death in the intramural ganglion cells of the guinea pig urinary bladder. The increased NADPH-d reactivity in such neurons suggests that nitric oxide may be involved in neuronal death in the urinary bladder following acute urinary retention.