Rabbit alveolar macrophages (RAMs) and cultured Chinese hamster ovary cells (CHOs) were exposed in vitro to the noncriteria pollutants manganese, cadmium, vanadium, nickel, lead, copper and cobalt, in either soluble or particulate form. To prevent the redistribution of soluble ions which occurs during conventional chemical fixation, methods of fixation by ultra-rapid freezing were developed which were applicable both to cells in suspension and to cell monolayers. Using chemical and freeze fixation, cellular and subcellular reactions to toxic elements were defined by both scanning and transmission electron microscopy. By exposing RAMs to red lead (Pb3O4), which is insoluble at pH 7 in tissue culture medium, it was shown that lead enters the cells through the phagosomal system and from that acid micro-enviroment is redistributed throughout the cytoplasm and nucleus. This system can be used as a model to study the movement of a toxic material on the surface of a particle within a lysosome into the interior of the cell.