In the Novel Fold category, three types of predictions were assessed: three-dimensional structures, secondary structures, and residue-residue contacts. For predictions of three-dimensional models, CASP4 targets included 5 domains or structures with novel folds, and 13 on the borderline between Novel Fold and Fold Recognition categories. These elicited 1863 predictions of these and other targets by methods more general than comparative modeling or fold recognition techniques. The group of Bonneau, Tsai, Ruczinski, and Baker stood out as performing well with the greatest consistency. In many cases, several groups were able to predict fragments of the target correctly—often at a level somewhat larger than standard supersecondary structures—but were not able to assemble fragments into a correct global topology. The methods of Bonneau, Tsai, Ruczinski, and Baker have been successful in addressing the fragment assembly problem for many but not all the target structures. Proteins 2001;Suppl 5:98–118. © 2002 Wiley-Liss, Inc.