HHpred is a fast and user-friendly server for protein homology detection and structure prediction, utilizing pairwise comparison of profile hidden Markov models (HMMs). It supports searches in various databases, including PDB, SCOP, Pfam, SMART, COGs, and CDD. Users can input a single query sequence or a multiple alignment, and HHpred returns results in a format similar to PSI-BLAST within minutes. Key features include local and global alignment options, scoring secondary structure similarity, and the ability to generate 3D structural models using MODELLER. The server aims to provide sensitivity comparable to powerful structure prediction servers while maintaining ease of use. A detailed help facility is available, and a demonstration using the SpoVT protein from Bacillus subtilis illustrates its capabilities. HHpred is accessible at http://protevo.eb.tuebingen.mpg.de/hhpred.HHpred is a fast and user-friendly server for protein homology detection and structure prediction, utilizing pairwise comparison of profile hidden Markov models (HMMs). It supports searches in various databases, including PDB, SCOP, Pfam, SMART, COGs, and CDD. Users can input a single query sequence or a multiple alignment, and HHpred returns results in a format similar to PSI-BLAST within minutes. Key features include local and global alignment options, scoring secondary structure similarity, and the ability to generate 3D structural models using MODELLER. The server aims to provide sensitivity comparable to powerful structure prediction servers while maintaining ease of use. A detailed help facility is available, and a demonstration using the SpoVT protein from Bacillus subtilis illustrates its capabilities. HHpred is accessible at http://protevo.eb.tuebingen.mpg.de/hhpred.