The goal of the present study has been to increase the statistical power, when scanning a genome sequence database with a regulatory motif, by taking advantage of additional sequence data from related species and from multiple sites within an intergenic region. We have extended Staden's method [10] to allow scanning of orthologous sequence data that are either multiply aligned, unaligned, or a combination of aligned and unaligned. Our new algorithm, PhyloScan, an extension of Staden's method, statistically accounts for the phylogenetic dependence of the species contributing data to the alignment and calculates a p-value for the sequence match in the aligned data set. This approach is similar to the MONKEY method [12]; however, there are several key differences between the two.