Abstract: Provided herein are in vitro methods for diagnosing an immediate hypersensitivity reaction (IHR) against a small compound or a drug in a subject, comprising the steps of (a) contacting mast cells with serum obtained from said subject; (b) contacting the mast cells obtained in step (a) with said small compound or said drug; (c) detecting mast cell activation and/or degranulation of the mast cells obtained in step (b); and (d) attributing the detection or no detection of mast cell activation and/or degranulation to a particular diagnosis of IHR.