We present DRUID (for Determination of Rates Using Intron Dynamics), a computational pipeline, for determining mRNA stability transcriptome-wide uses metabolic labeling and approach-to-equilibrium kinetics. Our pipeline uses endogenous introns to normalize time course data and yields more reproducible half-lives than other methods, even with datasets that were otherwise unusable. DRUID can handle datasets from a variety of organisms, spanning yeast to humans. Overall design: Transcription inhibition time courses (0, 1, 2, 4, 8, 12, 24 hr) using Actinomycin D or ?-amanitin were performed in HEK293 cells. Metabolic labeling time courses (1, 2, 4, 8, 12, 24 hr) using 4SU were performed in HEK293 and NIH3T3 cells. All experiments were performed in duplicate.