Aims: Smooth muscles from the urethra and internal anal sphincter (IAS) play an essential role in the maintenance of urinary and fecal continence. Any damage in these muscles may cause serious problems. The aim of this study was to directly compare the contractile properties of pig urethra and MS taken from the same animal. Methods: Smooth muscle strips of urethra and IAS dissected from the same pig were transferred to organ baths superfused with Krebs' solution, loaded with 1 g tension and equilibrated for 1 hr. Carbachol and phenylephrine response curves and EFS responses were elicited in the absence and presence of inhibitors. Results: Both tissues developed tone during the 1 hr equilibration period. Carbachol (3 x 10(-6)-10(-3)M) contracted urethra whilst relaxing IAS. Guanethidine (10(-6)M) inhibited the carbachol responses in both tissues. L-NOARG (10(-4)M) decreased carbachol responses in IAS, but not in urethra. Phenylephrine (3 x 10(-6)-10(-2)M) contracted both tissues. EFS (1-40 Hz) induced a contractile response in urethra which was decreased with guanethidine (10(-6)M) and further blocked by atropine (10(-6)M). In the presence of both, a relaxation response was observed that is sensitive to NOS inhibitors especially at low frequencies. EFS induced a relaxation followed by a contraction in IAS strips. This contraction was blocked by guanethidine but not by atropine, and the remaining relaxation at 20 Hz was decreased with L-NOARG and increased with L-arginine. Conclusions: There are differences between urethra and IAS in terms of muscarinic activation and neural innervation, relevant for pharmacotherapy. Neurourol. Urodynam. 29:1326-1331, 2010. (C) 2010 Wiley-Liss, Inc.