Our purpose was to define arteriolar network hemodynamics during moderate increases in interstitial adenosine or nitric oxide in the hamster (n = 34, pentobarbital sodium 70 mg/kg) cheek pouch tissue. The network consists of a feed arteriole (~12-µm diameter, ~800-µm length) with three to six branches. Observations of diameter, red blood cell flux, and velocity were obtained at the feed before the branch and within the branch. A comparison of baseline with suffused adenosine or sodium nitroprusside (SNP) 10⁹ to 10⁵ M showed the following. First, diameter change was heterogeneous by agonist, did not reflect the expected dilatory response, and was related to location within the network. With adenosine, upstream branch points constricted and those downstream dilated, even at 10⁵ M. With SNP, upstream branch points dilated, whereas those downstream constricted. Second, with adenosine, changes in diameter, flux, and velocity together resulted in no change in wall shear stress until 10⁵ M. Wall shear stress was not maintained at a constant level with N-nitro-L-arginine (10⁵ M), suggesting a role for flow-dependent diameter changes with adenosine. With SNP, diameter change correlated with the baseline (before SNP) shear stress conditions.