For several decades, the prevailing paradigm for modeling the effects of ionizing radiation (IR) on living systems was the target model with its inherent assumptions-that only those cells in the radiation path whose molecules sustained collisions with high energy particles and rays were damaged, that the damage was proportional to the energy absorbed by each cell and to the number of cells absorbing energy, and that all cells had identical sensitivities to radiation. However, evidence has accumulated that cells exhibit phenomena at low radiation exposures that appear to contradict at least one of these assumptions. Some of these phenomena currently under active study include low-dose hypersensitivity (HRS), increased radiation radioresistance (IRR), the adaptive response (AR), the bystander effect (BE), and death-inducing factor (DIE). These effects may interact to give rise to other phenomena such as hormesis, in which small amounts of otherwise toxic agent appear to be beneficial. Elucidating the cellular and molecular bases for these phenomena will lead to greater understanding of the relationships of these processes, including hormesis, to human health. (C) 2004 Published by Elsevier B.V.