In this study we present an accurate secondary structure prediction procedure by using an query and related sequences. The most novel aspect of our approach is its reliance on local pairwise alignment of the sequence to be predicted with each related sequence rather than utilization of a multiple alignment. The residue-by-residue accuracy of the method is 75% in three structural states after jack-knife tests. The gain in prediction accuracy compared with the existing techniques, which are at best 72%, is achieved by secondary structure propensities based on both local and long-range effects, utilization of similar sequence information in the form of carefully selected pairwise alignment fragments, and reliance on a large collection of known protein primary structures. The method is especially appropriate for large-scale sequence analysis of efforts such as genome characterization, where precise and significant multiple sequence alignments are not available or achievable.