The illicit use of beta-blockers in food-producing animals may induce the presence of these compounds in meat and milk. The presence of beta-blockers in these foods is a safety issue. A simple and economic high-performance liquid chromatography - tandem mass spectrometry method was developed and validated for beta-blockers in bovine and porcine muscle, kidney, liver, and bovine milk. The focus of the study was on the detection and quantitation of acebutolol, atenolol, betaxolol, carazolol, metoprolol, nadolol, penbutolol, and propranolol. Homogenized tissues were digested with glucuronidase/aryl sulfatase to release the analytes that were extracted with acetonitrile and purified using matrix solid-phase dispersion. For residues in milk, acidolysis and extraction utilized trichloroacetic acid and acetonitrile and the samples were purified using mixed-mode cation exchange solid phase extraction. Standard curves generated using homogenized tissues and milk matrices were linear with correlation coefficients exceeding 0.99. The limits of detection and quantification were 1 mu g/kg and 2.5 mu g/kg, respectively, for all analytes in the meat tissues. The corresponding values for milk were 0.2 mu g/kg and 0.5 mu g/kg. The average recoveries of the spiked samples were from 84.4 to 114.2% with the standard deviations of the intra- and inter-day assays from 2.0 to 14.6% and 2.9 to 18.7%, respectively. This method is simple, economical, and time-saving for the determination of beta-blockers in bovine tissue, porcine tissue, and bovine milk.