BACKGROUND: We evaluated whether spectral entropy (SpE) can measure the depth of hypnosis and the hypnotic drug effect in children during total intravenous anesthesia. METHODS: Sixty healthy children, aged 3-16 yr, were studied. Anesthesia was induced with an increasing target controlled infusion of propofol, and maintained by a stable remifentanil infusion and variable concentrations of target controlled infusion propofol. Depth of hypnosis was assessed according to the University of Michigan Sedation Scale (UMSS). Estimated plasma (C.P.) and pseudo effect site (Ceff) propofol concentrations reflected the hypnotic drug effect. Patients were stratified to three age groups. The correlations between SpE versus UMSS, C.P., and Ceff were analyzed by Prediction Probability (Pk). The pharmacodynamic relationship between SpE and C.P., and the differences of SpE values between the age groups at the corresponding UMSS levels, were studied. RESULTS: Respective mean Pk values for the youngest, middle, and oldest age groups were: 1) during induction: SpE versus UMSS 0.87, 0.87, and 0.93; SpE versus C.P. 0.92, 0.95, and 0.97; and SpE versus Ceff 0.88, 0.94, and 0.95; 2) during maintenance: SpE versus Ceff 0.86, 0.75, and 0.81. The pharmacodynamic analysis determined an association between SpE and C.P. that followed the Emax model closely. There were significant differences in SpE values between age groups at corresponding UMSS sedation levels. CONCLUSIONS: SpE measures the level of hypnosis and hypnotic drug effect in children during total intravenous anesthesia. There is an age dependency associated with SpE. Anesthesia should not be steered solely on the basis of SpE.