The effect of particle size on the percent drug absorbed is computationally modeled for controlled-release dosage forms that deliver drug particles to the colon. The relative benefit of reducing particle size is mapped on a diagram of the drug's absorption rate constant (estimated from rat intestinal perfusion, CACO-2 or human intubation permeation rates) versus the drug's solubility. Some drugs fall into a limit of high percentage absorption even with large particles such that particle size reduction has little impact. Another group of drugs is solubility limited such that even with small particles, absorption is negligible. Between the two regions, only drugs with sufficiently high absorption rates are influenced by the drug dissolution rate and thereby the particle size. The size of this region is a function of dosing rate. Comparisons between calculated particle size effects on colon absorption as a function of colon volume suggest caution when using animal models to predict bioavailability from colonic drug delivery. This volume dependence also suggests that the particle size influence will vary as a function of the digestive cycle.