Stimulation of cells with soluble growth regulatory factors, as well as interactions with molecules of an adjacent cell or components in the extracellular matrix, initiate different signal transduction pathways inside the cell. An important aspect of the regulation of such pathways is the interactions between signaling molecules, mediated by conserved domains, such as SH2, SH3, PTB and WW (reviewed in Refs 1, 2). These domains mediate protein-protein interactions by binding to short peptide motifs containing phosphorylated tyrosine residues (SH2 and PTB domains) or proline-rich regions (SH3 and WW domains). Recently, another conserved domain that interacts with the carboxy-terminal ends of target proteins has been identified and named PDZ. PDZ domains were originally identified in the post-synaptic density protein PSD-95 as three repeats of about 90 residues containing the conserved motif Gly-Leu-Gly-Phe (GLGF) 3. The name PDZ domain is derived from the names of three proteins containing such domains [PSD-95, the Drosophila discs-large tumor suppressor protein DlgA (Ref. 4) and the tight junction protein Z__O-1 (Ref. 5)]; alternative designations are GLGF-repeat and DlgA homology region, DHR. PDZ domains have now been identified in a variety of proteins 6 that are often found in structures at the plasma membrane and are involved in signal transduction pathways. Here, we discuss some known and anticipated interactions between PDZ domains and target proteins, as well as the structural requirements for interactions between PDZ domains and target proteins.