Meta-BASIC (http://basic.bioinfo.pl) is a novel sensitive approach for recognition of distant similarity between proteins based on consensus alignments of meta profiles. Specifically, Meta-BASIC compares sequence profiles combined with predicted secondary structure by utilizing several scoring systems and alignment algorithms. In our benchmarking tests, Meta-BASIC outperforms many individual servers, including fold recognition servers, and it can compete with meta predictors that base their strength on the structural comparison of models. In addition, Meta-BASIC, which enables detection of very distant relationships even if the tertiary structure for the reference protein is not known, has a high-throughput capability. This new method is applied to 860 PfamA protein families with unknown function (DUF) and provides many novel structure-functional assignments available on-line at http://basic.bioinfo.pl/duf.pl. Detailed discussion is provided for two of the most interesting assignments. DUF271 and DUF431 are predicted to be a nucleotide-diphospho-sugar transferase and an alpha/beta-knot SAM-dependent RNA methyltransferase, respectively.