Responding to a demonstrated need for scientists to forecast the permeability and bioavailability (F) properties of compounds before their purchase, synthesis, or advanced testing, we have developed a score that assigns the probability that a compound will have F > 10% in the rat. Neither the rule-of-five, log P, log D, nor the combination of the number of rotatable bonds and polar surface area successfully categorized compounds. Instead, different properties govern the bioavailability of compounds depending on their predominant charge at biological pH. The fraction of anions with >10% F falls from 85% if the polar surface area (PSA) is < or = 75 A(2), to 56% if 75 < PSA < 150 A(2), to 11% if PSA is > or = 150 A(2). On the other hand, whereas 55% of the neutral, zwitterionic, or cationic compounds that pass the rule-of-five have >10% F, only 17% of those that fail have > 10% F. This same categorization distinguishes compounds that are poorly permeable from those that are permeable in Caco-2 cells. Further validation is provided with human bioavailability values from the literature.