ABSTRACT. Objectives. To determine whether the commonly used over-the-counter medications dextromethorphan and diphenhydramine are superior to placebo for the treatment of nocturnal cough and sleep difficulty associated with upper respiratory infections and to determine whether parents have improved sleep quality when their children receive the medications when compared with placebo.Methods. Parents of 100 children with upper respiratory infections were questioned to assess the frequency, severity, and bothersome nature of the nocturnal cough. Their answers were recorded on 2 consecutive days, initially on the day of presentation, when no medication had been given the previous evening, and then again on the subsequent day, when either medication or placebo was given before bedtime. Sleep quality for both the child and the parent were also assessed for both nights.Results. For the entire cohort, all outcomes were significantly improved on the second night of the study when either medication or placebo was given. However, neither diphenhydramine nor dextromethorphan produced a superior benefit when compared with placebo for any of the outcomes studied. Insomnia was reported more frequently in those who were given dextromethorphan, and drowsiness was reported more commonly in those who were given diphenhydramine.Conclusions. Diphenhydramine and dextromethorphan are not superior to placebo in providing nocturnal symptom relief for children with cough and sleep difficulty as a result of an upper respiratory infection. Furthermore, the medications given to children do not result in improved quality of sleep for their parents when compared with placebo. Each clinician should consider these findings, the potential for adverse effects, and the individual and cumulative costs of the drugs before recommending them to families. Pediatrics 2004;114:e85-e90. URL: http://www.pediatrics.org/cgi/content/full/114/ 1/e85; cough, upper respiratory infection, dextromethorphan, diphenhydramine, placebo.