In this study, a three-stage process consisting of mechanical milling, heat treatment, and washing has been used to manufacture nanoparticulate ZnO powders with a controlled particle size and minimal agglomeration. By varying the temperature of the post-milling heat treatment, it was possible to control the average particle size over the range of 28–57 nm. The photocatalytic activity of these powders was characterized by measuring the hydroxyl radical concentration as a function of irradiation time using the spin-trapping technique with electron paramagnetic resonance spectroscopy. It was found that there exists an optimum particle size of approximately 33 nm for which the photocatalytic activity is maximized. The existence of this optimal particle size is attributable to an increase in the charge carrier recombination rate, which counteracts the increased activity arising from the higher specific surface area for a sufficiently small particle size.