This study sought to determine whether saliva concentrations of morphine correlate with plasma levels of morphine in pediatric patients receiving morphine analgesia for severe pain, and to evaluate whether the measurement of saliva morphine concentrations would be a useful, noninvasive, clinical tool to diagnose systemic exposure to morphine. Fifteen pediatric patients were enrolled; for the control group, 18 adult volunteers were recruited. Patients received continuous morphine drips to ameliorate pain caused by a sickle cell vasoocclusive crisis (range, 10-40 µg/kg·h). Control subjects were randomized into those receiving acetaminophen with either 8 mg (n = 13) or 30 mg (n = 5) of codeine. All participants fasted at least 2 hours before sample collection. Blood and saliva samples were collected simultaneously. All samples were analyzed by radioimmunoassay for morphine. There was no correlation between saliva and plasma morphine concentrations in either the patients receiving intravenous morphine (r = 0.04, P = 0.89) or in the controls receiving codeine (r = 0.43, P = 0.08). There was no observed difference in the mean counts per minute (CPM) for saliva samples in the pH range 3.96 to 8.06. Saliva concentrations of morphine cannot be used to predict the plasma concentration of morphine in children or adults. However, the concentration of morphine in saliva may be used as a qualitative indicator of systemic exposure to morphine in a subject.