There is evidence to suggest an abnormality of the colonic myenteric plexus in severe chronic constipation. The present study investigates whether this abnormality involves functional changes in the cholinergic innervation of human colon. Human taenia coli muscle strips (taenia), previously incubated with [3H]choline to radiolabel neuronal stores of acetylcholine, were subjected to electrical field stimulation (1 Hz or 10 Hz, 1 ms, 480 pulses at 200 mA). The stimulation evoked release of tritiated material, shown previously to accurately represent neural [3H] acetylcholine release, was depressed in tissue from constipated compared with non-constipated patients. Evoked release of tritiated material was reduced by storage of the taenia at 4 degrees C or by increasing the frequency of stimulation, but increased by stimulation during incubation with [3H]choline. The results indicate that reduced activity of cholinergic nerves may occur within the bowel wall of colon removed for severe chronic constipation.