RATIONALE Isocyanates are highly reactive species widely used in industry. They can cause irritation of the eyes, trigger asthma, etc. Polychlorinated biphenyls (PCBs) were widely used in electrical equipments like capacitors and transformers in the last century and are still present in the environment today. PCBs are known to cause cancer and to affect the immune, reproductive, nervous and endocrine systems. Therefore, there is a need for a simple, rapid and reliable analytical method for the detection of traces of isocyanates and of PCBs. METHODS The data presented in this paper were obtained using a proton transfer reaction (PTR) time‐of‐flight mass spectrometer and a high sensitivity PTR quadrupole mass spectrometer. We also utilized a recently developed direct aqueous injection (DAI) inlet system for proton transfer reaction mass spectrometry (PTR‐MS) instruments that allows the analysis of trace compounds in liquids. RESULTS We detected four isocyanates in the headspace above small sample quantities and investigated their fragmentation pathways to obtain a fundamental understanding of the processes involved in proton transfer reactions and also to determine the best operating conditions of the PTR‐MS instruments. In addition, nine PCBs were unambiguously identified via their exact mass and isotopic distribution and detected in different concentration levels via direct injection of the liquid. CONCLUSIONS Utilizing recent developments and improvements in PTR‐MS, we can rapidly detect two important environmental pollutant compound classes (isocyanates and PCBs) at high accuracy and without any sample preparation. In this paper, we provide proof of the detection of traces of isocyanates and PCBs in air and also of PCBs in liquids. These results could be used for the development of a real‐time monitoring device for industrial waste, polluted air or water quality surveillance. Copyright © 2012 John Wiley & Sons, Ltd.