Intercellular communication through aqueous intercellular channels, known as gap junctions, has been postulated to provide an important mechanism for coordinating the rapid and synchronous responses of corporal smooth muscle during human penile erection and detumescence. Mathematical modeling analyses of drug diffusion were utilized to examine the potential physiological importance of the intercellular pathway to the regulation of smooth muscle tone in the human corpus cavernosum. In addition, patch clamp analyses and optical imaging studies were conducted to assess the ionic basis for cellular excitability and homeostasis in cultured corporal smooth muscle cells. In short, the computer modeling studies demonstrated that intercellular communication through gap junctions is likely to be the 'preferred' pathway for coordination of cellular activation and syncytial smooth muscle responses in this tissue. Moreover, the observed ion channel diversity reveals even further complexities to the modulation of corporal smooth muscle tone.