Many pharmaceutical compounds have been detected in surface waters, but their effects on stream ecosystem function are not currently understood. Concentrations of cimetidine, a widely used antihistamine, have increased in streams and rivers. Invertebrates may be affected by exposure to cimetidine because they use histamines to regulate olfactory and stomatogastric function. Primary producers, such as algal biofilms, also may be affected by cimetidine, which may in turn, alter metabolism and ultimately invertebrate population dynamics. We conducted a long-term (83 d) experiment in artificial streams to measure the chronic effects of cimetidine on benthic biofilm function and stream invertebrate growth and population dynamics. We exposed 2 common invertebrate species, Gammarus fasciatus and Psephenus herricki, and biofilm to concentrations of cimetidine similar to what is found in USA surface waters (0.07–70.0 µg/L). We found no consistent effect of cimetidine on biofilm chlorophyll a or function (gross primary production, respiration). Growth and final biomass of reproducing G. fasciatus was reduced across all cimetidine treatments compared to the control. In addition, no individuals of the smallest size class occurred at lower concentrations of cimetidine suggesting that cimetidine may either more strongly affect invertebrates of smaller size classes or may suppress adult reproduction. We also found that higher concentrations of cimetidine significantly reduced survivorship of P. herricki. Low concentrations of cimetidine appear to have no effect on primary producers, but our observations indicate there are indirect negative effects on invertebrate growth and population dynamics.