The protein loop, a novel category of nonregular secondary structure, is a segment of contiguous polypeptide chain that traces a "loop-shaped" path in three-dimensional space; the main chain of an idealized loop resembles a Greek omega (omega). A systematic study was made of 67 proteins of known structure revealing 270 omega loops. Although such loops are typically regarded as "random coil," they are, in fact, highly compact substructures and may also be independent folding units. Loops are almost invariably situated at the protein surface where they are poised to assume important roles in molecular function and biological recognition. They are often observed to be modules of evolutionary exchange and are also natural candidates for bioengineering studies.