The propagation of urine from the kidney is initiated by the pacemaker activity in the renal pelvis (1-2). The density of cholinergic nerve fibers in the ureter increases from renal pelvis to the bladder with the ureterovesical junction being the most densely innervated region. The difference in contractile behavior between the upper, middle & lower ureteric segments is not well understood in response to cholinergic modulators. This study investigates the contractile behavior of the different ureteric segments of the pig and the effect of cholinergic-receptor modulators. Ureters were isolated from freshly slaughtered pigs (6 to 8 months old). Three centimeter longitudinal strips of upper (UU), middle (MU) and lower ureter (LU) were suspended in 25 ML organ baths containing Krebs bicarbonate solution, maintained at 37°C & gassed with 95% O2 & 5% CO2. Tissue tension was measured using isometric force transducers connected to a PowerLab data acquisition system using ‘Chart’ software. Tissue segments were equilibrated under 2g of tension for 60 min and assessed for basal spontaneous activity (BSA). Tissues without BSA were discarded. Amplitude and frequency of BSA were compared between different ureteric segments. The effect of cholinergic-receptor modulators, carbachol (CCh, 10 µM) and atropine (AT) (1µM) (10-15 min exposure to each drug), on BSA of UU, MU & LU was then investigated. All data is expressed as the mean ± SEM. Statistical analysis was performed using one-way ANOVA and Student’s paired t-tests. Results 100% of UU (n=23), 65% of MU (n=24) & 65% of LU (n=24) segments demonstrated BSA. The amplitude of BSA in the LU (0.028±0.003 g tension/mg tissue) was significantly (p<0.001) higher than MU (0.015±0.002 g tension/mg tissue) & UU (0.009±0.002 g tension/mg tissue). However, the frequency of BSA was significantly (p<0.001) higher in UU (25.09±2.07 events in 5min) vs. MU (3.08±0.68 events in 5 min) and LU (3.63±0.78 events in 5min) segments. 10µM CCh significantly (p<0.01-0.001) enhanced the amplitude and the frequency of BSA in MU (n=13) & LU (n=17) segments, however it did not affect the BSA of UU (n=16). 1µM AT reduced the amplitude of BSA in MU (n=13) & LU (n=14), (although not statistically significant), with no effect on the UU (n=12) segments. The pattern of BSA was significantly different in UU, LU and MU segments. The frequency of BSA was significantly higher in UU compared to LU and MU strips. In contrast, the amplitude of BSA was significantly higher in the LU compared to MU and UU segments, demonstrating that each segment plays a different role in mediating the peristaltic movement of the ureter. The differences in the sensitivity of different ureteric segments to cholinergic-receptor manipulation can provide a better understanding of ureteric pharmacology and aid development of a targeted approach in the management of ureteric conditions.