The single-dose prediction model (SDPM) of Slattery et al. has been shown accurately to predict short-term (3 to 7 days) steady-state valproic acid (VPA) concentrations in normal volunteers and in hospitalized patients receiving monotherapy. To assess the long-term usefulness of the SDPM in a real-life clinic setting, six ambulatory patients ranging in age from 2 to 8 years were studied. Blood samples were drawn at least 6 h after the initial dose but before the second dose of VPA, A steady-state trough concentration (Cminss) was measured 3 to 7 days after the initiation of therapy. Dosage adjustments and alterations in therapeutic regimen were allowed and another Cminss was measured after 1 to 12 months. Predicted Cminss values were calculated for both the short-term and long-term VPA regimens. Predictive performance analysis demonstrated that the SDPM was unbiased in predicting both short-term and long-term VPA Cminss values and precise in predicting only short-term VPA Cminss values. The SDPM is not a reliable predictor of long-term total VPA concentrations in seizure patients in an outpatient clinic setting.