Pharmaceutical compounds have been detected in urban streams throughout the U.S.; however, their effects on stream ecosystems are understudied.  Cimetidine (Tagamet®), an H₂ histamine antagonist, has been detected nationwide and regulates invertebrate olfactory and stomatogastric systems. We predicted that cimetidine may affect stream-dwelling invertebrates.  Although cimetidine has been detected in surface waters, the effects on aquatic organisms have not been studied.  We dosed 30 artificial streams with 4 concentrations of cimetidine and measured its effects on Psephinus herricki and Gammarus fasciatus.  We measured mortality over 12 weeks and instantaneous growth rates over 3 weeks.  Cimetidine increased mortality of P. herricki, but did not affect G. fasciatus mortality. In contrast, the highest concentration of cimetidine decreased G. fasciatus growth, but did not affect P.herricki growth.   Effects of cimetidine were taxa specific, which emphasizes the complexity of examining effects of novel contaminants.  In addition, we monitored cimetidine concentrations throughout the study using our new HPLC technique.  Cimetidine bound readily to organic matter and suggests exposure was through feeding not water.  Our methods examining the effects long-term chronic exposure on growth and mortality may be well-suited to investigations of novel compounds found in low concentrations, such as pharmaceuticals.