Since the classical studies of Holtfreter (1948), the generation and maintenance of tissue diversity during embryonic development have been explained on the basis of differential affinities between cells. More recently, it has been both reasonable and fashionable to describe such differences in terms of the selective expression of cell-cell adhesion systems (Nose et al., 1988; Jaffe et al., 1990). But variation by adhesion is not the only way to change cell affinities. It may, for example, be required in vivo to create and sustain discontinuities or boundaries between neighboring cell populations; but is it sufficient? Taking a cue from recent findings in the nervouqsystem, we argue here that active cell-cell repulsion should also be considered as a possible morphogenetic mechanism. Growth Cone Collapse Several studies on axon guidance have reported that the motile tip of growing axons, the growth cone, can undergo a dramatic change in shape (from a spread to collapsed state) and behavior (temporary cessation of motility) in response to particular environmental signals (see Figure 1). This was first described clearly by Kapfhammer and Raper (1987), who showed that growth cones derived from peripheral neurons collapse in vitro when they contact axons derived from central neurons, and vice versa. These authors recognized that it was difficult to explain the collapse solely by invoking changes in adhesive properties of the cells concerned. A direct extension of this elegant work has been the development of a quantitative in vitro assay for the presence in vivo of molecules that are responsible for mediating such effects (Raper and Kapfhammer, 1990). The application of the assay to the problem of peripheral nerve segmentation has reinforced the relevance of the collapse phenomenon for explaining a normal biological process. In higher vertebrate embryos, outgrowing spinal axons traverse exclusively the anterior half-somite (Keynes and Stern, 1984), and a strong case can be made for the existence of a molecular system that mediates repulsion between growth cones and cells of the posterior half-somite. In the chick, the lectin peanut agglutinin binds to the surfaces of posterior but not anterior cells. Exploiting this fact, Davies at al. (1990) have now isolated a peanut agglutinin binding glycoprotein fraction from chick somites, and shown that it has potent collapse-inducing activity in the assay. This activity may be mirrored, albeit on a lesser scale, in vivo. It may be enough, for example, for a single filopodium to respond to the repellent stimulus on posterior cells in order to inform the parent growth cone that it is approaching a “no-go” area. A further example of growth cone repulsion has been Minireview