AbstractIn this work we evaluate the cartical expansion model for amoeboid chemo‐taxis with regard to new information about molecular events in the cytoskeleton following chemo‐tactic stimulation ofDictyosteliumamoebae. A rapid upshift in the concentration of chemoattrac‐tant can be used to synchronize the motile behavior of a large population of cells. This synchrony presents an opportunity to study the biochemical basis of morphological changes such as pseudopod extension that are required for amoeboid chemotaxis. Changes in the composition and activity of the cytoskeleton following stimulation can be measured with precision and correlated with important morphological changes. Such studies demonstrate that activation of actin nucleation is one of the first and most crucial events in the actin cytoskeleton following stimulation. This activation is followed by incorporation of specific actin cross‐linking proteins into the cytoskeleton, which are implicated in the extension of pseudopods and filopods. These results, as well as those from studies with mutants deficient in myosin, indicate that cortical expansion, driven by focal actin polymerization, cross‐linking and gel osmotic swelling, is an important force for pseudopod extension.It is concluded that whereas three forces, frontal sliding, tail contraction, and cortical expansion may cooperate to produce amoeboid movement, the cortical expansion model offers the simplest explanation of how focal stimulation with a chemoat‐tractant causes polarized pseudopo