Large numbers of protein-protein interactions have been mapped for yeast and worms, and now in the January 11 Nature, Rain et al. present the first large set of interactions for a prokaryote (Nature 2001, 409:211-215). The two-hybrid screen of 261 proteins from the gastric pathogen Heliobacter pylori against a library of genome-encoded polypeptides revealed 1,200 putative interactions. Screening against a library allows the identification of interacting domains, and reduces the rate of false negatives encountered in classical pair-wise screens. A strong selection protocol reduces the number of false positives. Rain et al. also use a probability score to compute the likelihood that a given two-hybrid result is a consequence of background noise, and use some of the identified interactions to assign various proteins to particular biological pathways.