Background and Purpose: Intraluminal application of pharmacologic agents for acute ureteral dilation may facilitate difficult ureteroscopy. We characterized the in-vivo effects of intraluminal application of verapamil and theophylline on ureteral peristalsis and diameter in a porcine model. Materials and Methods: Twenty-four female domestic pigs (35-40 kg) were incorporated into the study. We deployed a giant magneto resistive (GMR) sensor and electromagnetic (EMG) electrodes laparoscopically onto the ureteral surface for simultaneous measurement of the mechanical and electrical signals of ureteral peristalsis, respectively. The ureteral-luminal diameter was measured at three levels by digital retrograde pyelography and standardized to a 10-mm laparoscope. The results were calculated as change in peristalsis and ureteral diameter from baseline during the first hour after drug injection. We tested two smooth-muscle relaxants, verapamil (2 mg/kg) and theophylline (70 mg/kg), with saline and dimethylsulfoxide (DMSO; solvent) as controls. Six pigs were studied for each of the four groups. Hydration, anesthesia, and intra-abdominal pressure were standardized. The serum concentrations of the drugs were measured to determine systemic absorption. Results: During the first 10 minutes after intraluminal drug injection, theophylline caused a significant decrease in ureteral peristalsis (6.75 waves/10 minutes) compared with the control group (1.00/10 minutes; P = 0.02). This trend persisted for the next hour. However, there were no changes from baseline in ureteral width. Ureteral peristalsis and dilation remained similar after the saline and DMSO injections. Verapamil increased the diameter of the proximal ureter compared with the controls throughout the hour after drug injection. Fifteen minutes after the drug injection, the change in the ureteral diameter with verapamil was 1.38 mm (4.14F), while the control group showed a change of 0.27 mm (P = 0.03). At 1 hour, the width of the proximal ureter in the verapamil group had increased by 1.72 mm (5.16F), while the control group had changed by 0.55 mm (P = 0.03). There were no statistically significant changes in the widths of the mid or distal ureter. No ureteral dilation was observed in the other groups. Conclusions: In the porcine model, intraluminal application of pharmacologic agents produced independent effects on ureteral dilation and peristalsis. Theophylline inhibited ureteral peristalsis, and verapamil produced acute proximal-ureteral dilation. The ability to alter ureteral diameter or peristaltic activity acutely may facilitate ureteroscopy.