Human peripheral lymphocytes can be transformed by treatment with galactose oxidase alone. Prior treatment with neuraminidase enhances this effect. The aldehyde blocking agents thiocarbohydrazide, hydroxylamine, dimedone, and sodium borohydride block transformation when they follow, but not when they precede, galactose oxidase treatment. Thus, as is the case for periodate-induced lymphocyte transformation, the formation of free aldehyde at the cell surface would seem to be a critical event in the triggering of transformation by this agent. The degree of transformation is highly variable from individual to individual, and also for the same donor at different times. However, the lymphocytes of some people give a consistently poor response to galactose oxidase. Similar results have been obtained for periodate-induced transformation of human lymphocytes, but to date this is unexplained.