The general transcription factor TFIID is composed of the TATA box binding protein (TBP) and multiple TBP-associated factors (TAFs) [1–3]. In yeast, promoters can be grouped into two classes based on the involvement of TAFs [4, 5]. TAF-dependent (TAF_dep) promoters require TAFs for transcription, and TBP and TAFs are present at comparable levels on these promoters. TAF-independent (TAF_ind) promoters do not require TAFs for activity, and TAFs are either absent or present at levels far below those of TBP on these promoters. Here, we demonstrate that the upstream activating sequence (UAS) mediates the selective recruitment of TAFs to TAF_dep promoters. A TAF_ind UAS fails to recruit TAFs and to direct efficient transcription when inserted upstream of a TAF_dep core promoter. This transcriptional defect can be overcome by a potent activator, indicating that a strong activation domain can compensate for the absence of TAFs on a TAF_dep core promoter. Our results reveal a requirement for compatibility between the UAS and core promoter and thus help explain previous reports that only certain yeast UAS-core promoter combinations and mammalian enhancer-promoter combinations are efficiently transcribed [6–11]. The differential recruitment of TAFs by UASs provides strong evidence for the proposal that in vivo TAFs are the targets of some, but not all, activators.