In eukaryotes, activation of transcription involves an interplay between activators bound to cis-regulatory elements and factors bound to basal elements near the start site of transcription. The basal elements, for example the TATA box or proximal sequence element (PSE) of small nuclear RNA (snRNA) promoters, nucleate the assembly of basal transcription complexes, components of which interact with activators. Although one basal transcription complex can interact with many activators, it is unclear whether different basal transcription complexes can direct different responses to particular activators. We show here that changing the arrangement of basal elements can alter the response to transcriptional activation domains. Indeed, in the human U6 snRNA promoter, point mutation of either a TATA box or PSE results in diametrically opposed responses to VP16- and Sp1-derived activation domains. These basal elements can even discriminate small changes in an activation domain. Thus the arrangement of basal promoter elements provides a mechanism for differential regulation of transcription.