There are at least two possible explanations for the observation that inoculation with a single microorganism is generally insufficient to cause infection while inoculation with many organisms may regularly result in infection in a susceptible host. Microorganisms may act cooperatively, with the occurrence of infection resulting from their joint action. Alternatively, each organism of the infecting inoculum may independently possess the potential to cause infection, and, with an inoculum size approximating the 50% infectious dose, infection may result from the survival and multiplication of a single organism. Several lines of experimental data involving several bacterial species strongly support the independent-action, or "single-organism," hypothesis of the pathogenesis of colonization and infection. Available data also support the independent-action hypothesis in the pathogenesis of experimental viral infections. This hypothesis provides an explanation for the occurrence of sporadic episodes of infection.