Recent advances in techniques that allow sensitive and specific measurement of S-nitrosothiols (RSNOs) have provided evidence for a role for these compounds in various aspects of nitric oxide (NO) biology. The most widely used approach is to couple reaction chemistry that selectively reduces RSNOs by one electron to produce NO, with the sensitive detection of the latter under anaerobic conditions using ozone based chemiluminescence in NO analyzers. Herein, we report a novel reaction that is readily adaptable for commercial NO analyzers that utilizes hydrogen sulfide (H2S), a gas that can reduce RSNO to NO and, analogous to NO, is produced by endogenous metabolism and has effects on diverse biological functions. We discuss factors that affect H2S based methods for RSNO measurement and discuss the potential of H2S as an experimental tool to measure RSNO. © 2008 Elsevier Inc. All rights reserved.