We investigate the relationship between passive permeability and molecular size, in the context of solubility-diffusion theory, using a diverse compound set with molecular weights ranging from 151 to 828, which have all been characterized in a consistent manner using the RRCK cell monolayer assay. Computationally, each compound was subjected to extensive conformational search and physics-based permeability prediction, and multiple linear regression analyses were subsequently performed to determine, empirically, the relative contributions of hydrophobicity and molecular size to passive permeation in the RRCK assay. Additional analyses of Log D and PAMPA data suggest that these measurements are not size selective, a possible reason for their sometimes weak correlation with cell-based permeability.