Numerous genomic and proteomic datasets are permitting the elucidation of transcriptional regulatory networks in the yeast Saccharomyces cerevisiae. However, predicting the condition dependence of regulatory network interactions has been challenging, because most protein-DNA interactions identified in vivo are from assays performed in one or a few cellular states. Here, we present a novel method to predict the condition-specific functions of S. cerevisiae transcription factors (TFs) by integrating 1327 microarray gene expression data sets and either comprehensive TF binding site data from protein binding microarrays (PBMs) or in silico motif data. Importantly, our method does not impose arbitrary thresholds for calling target regions 'bound' or genes 'differentially expressed', but rather allows all the information derived from a TF binding or gene expression experiment to be considered. We show that this method can identify environmental, physical, and genetic interactions, as well as distinct sets of genes that might be activated or repressed by a single TF under particular conditions. This approach can be used to suggest conditions for directed in vivo experimentation and to predict TF function.