The Eph family of receptor tyrosine kinases and their 'ligands', the ephrins, have been implicated in a large number of developmental processes, such as boundary formation, cell migration, axon guidance and vasculogenesis. A characteristic of the EphB subclass is that both EphBs and transmembrane-anchored ephrin-Bs function as receptors and as ligands, a phenomenon commonly described as 'bi-directional signalling'. Here we review recent data indicating that EphA receptors and glycosylphosphatidylinositol (GPI)-anchored ephrin-As can also mediate bi-directional signalling. Moreover, characterization of the expression of ephrin-As on axons of the retinotectal and vomeronasal projections suggests that the EphA subfamily is involved in both repulsive and attractive guidance mechanisms during establishment of neuronal connections.