A set of genes (SWI1, SWI2/SNF2, SWI3, SNF5 and SNF6) in Saccharomyces cerevisiae are required for transcription of a variety of yeast genes. It was recently reported that the mammalian glucocorticoid receptor failed to activate transcription when transiently expressed in swi1, swi2 or swi3 yeast strains. We report here that two highly related human cDNAs, hSNF2α and -β, encode amino acid sequences homologous to both the yeast SWI2/SNF2 and the Drosophila brahma. Similar to their yeast and Drosophila counterparts, both human cDNAs contain helicase motifs, a bromodomain, a highly charged C-terminal sequence and an N-terminal sequence rich in proline, glutamine and glycine. Tissue distribution of the mRNAs varied slightly. Transcriptional activation by the estrogen receptor and the retinoic acid receptor was enhanced by co-expression of either hSNF2 cDNA. No enhancement was observed for promoters which do not respond to nuclear receptors. We suggest that global transcriptional coactivators equivalent to the yeast SWI/SNF complex exist in mammalian cells.