While many high-throughput screening campaigns involve the measurement of protein levels or locations, at times it is desirable to measure the levels of gene expression in response to small molecules. Here, we describe a method for capturing mRNA in multiwell plates following compound treatment and measuring gene expression using real-time PCR. This streamlined protocol provides complementary information to conventional phenotypic cell-based assays, and is especially useful in cases where the gene of interest is thought to serve a regulatory function in downstream cellular phenotypes.