The effect of cell density on the sensitivity of tumor cells to selenite has been examined. The inhibitory effect of selenite on cellular DNA and RNA synthesis was significantly greater in higher density cultures of HeLa cells and A2780 ovarian tumor cells. High-density cells were also more sensitive to the inhibitory effect of selenite on cell attachment. This difference could not be accounted for by a higher intracellular level of glutathione, since there was no significant difference between the cells at high or low density. The high-density cells were found to take up more selenium per cell during the exposure period; the resulting higher level of intracellular Se could explain their greater sensitivity to selenite. This hypothesis is supported by the observation that DNA synthesis in nuclei isolated from high-density cells did not exhibit higher sensitivity to inhibition by selenite than synthesis in nuclei isolated from low-density cells.