In this review, I consider the quantitative consequences of the diffusion of free NO in determining its biological actions. Several studies have measured the extent to which NO diffuses away from an NO-producing cell, and the distance of its diffusion is quite large, on the order of 100-200 microm. This wide diffusibility is consistent also with the high value for its diffusion constant, 3300 microm2/s. Mathematical simulations based on this wide diffusibility suggest that, within spatial limits of approximately 0.3-0.4 mm, the actions of free NO are dictated by the total number of NO-producing cells within this location as opposed to where the NO-producing cells are located within this space. These results suggest that the actions of NO are surprisingly long range and the diffusion of NO is an important determinant of its biological actions. Thus, the effects of NO on individual target cells may be determined more by each cell's preprogrammed characteristic response to NO than by proximity to an NO source. In addition, scavenging of NO by hemoglobin in blood vessels should represent a significant sink for its scavenging, posing difficulty for the postulate that only free NO functions as EDRF.