MANY EXTRACEILULAR PROTEINS, including cell-surface receptors, extracellular matrix molecules and members of the blood coagulation cascade and complement system, contain multiple copies of commonly occurring structural modules. Since many of these proteins are involved in adhesive processes, the major role of these protein modules is probably the mediation of protein-protein interactions. These motifs are often encoded by single exons and gene rearrangements and duplication are responsible for their wide dlstributlon. As a consequence, intronexon boundaries of a single phase class predominate in the resulting genes]. As a rule, shuffled modules are flanked by phase 1 introns splitting the reading frame between the first and second nucleotides of the codon (class 1-1 modules). A hallmark of many of these protein modules is the conservation of cysteine residues that stabilize their tertiary structure by forming intramolecular disulfide bridges. Typical examples are the short consensus repeat of many complement regulatory proteins, the kringle structure and epidermal growth factor (EGF)-Iike repeatsL Within the last few years a new cysteine-rich module has been discovered in a variety of proteins. This module is known as either the trefoil motif 2 or the P-domain3; we will use the latter term in this review. w, Hoffmann and F, Hauser are at the