Pharmaceuticals have been found at low concentration in streams around the world but little is known about potential environmental effects of these emerging contaminants.  Ten headwater streams in the Upper White River Watershed of central IN, USA, were sampled for trace pharmaceuticals in conjunction with measurements of water quality.   Four pharmaceuticals, 1,7-Dimethylxanthine (caffeine metabolite), acetaminophen, caffeine, and cotinine (nicotine metabolite) were found at one or more sites with mean concentrations of 0.038, 0.109, 0.057 and 0.041 µg/L respectively.  Caffeine was ubiquitous with trace concentrations measured at all sites.  Stream pH was correlated with 1,7-dimethylxanthine (p = 0.05), acetaminophen (p = 0.06), and caffeine (p = 0.07).  Nitrate concentrations were correlated with 1,7-dimethylxanthine (p < 0.05) and caffeine (p < 0.05).  An in situ experiment was also conducted using nutrient diffusing substrata where cellulose sponges were placed on pharmaceutical-amended (acetaminophen, ibuprofen, caffeine, and nicotine) agar and incubated in-stream for 14 d followed by measurements of microbial colonization (change in dry mass) and respiration (dehydrogenase enzyme activity).  Microbial respiration did not significantly change with pharmaceutical treatment.  Our results demonstrate that nonprescription pharmaceuticals are common in Indiana streams and they may influence microbial activity.