When single cells were allowed to attach to circular islands of adhesive substratum, their proliferation was strongly dependent on island area over the range 500 micron2 to 5000 micron2. The number of freshly explanted whole mouse embryo fibroblasts that performed DNA synthesis corresponded closely with a simple geometrical measure of area of cell surface exposed to the medium: freely suspended cells were only slightly less stimulated than attached cells exposing an equal surface area; hemispherical cells were less stimulated than cells of any other shape. In contrast, 3T3 cells were stimulated sixfold by islands too small to allow any increase in area. These experiments show that anchorage can stimulate by two different mechanisms. They offer a general method of measuring substrate contact stimulation.