In experiments in which mammalian cells were irradiated with 5 . 6 MeV alpha particles from a Tandem Van de Graaff machine, we have confirmed the finding of others that the mean lethal dose (Do) is about 60 rad. However, on measuring the area of the nuclei of the flattened cells as they were irradiated, we found that this mean lethal dose corresponds to the passage of not one or two alpha particles per cell nucleus as expected but to between 10 and 20 particles. This allows for the possibility that the direct action of alpha particles on the nucleus may be the important event in carcinogenesis.