Methadone, when used in the appropriate dose, prevents opioid withdrawal during the 24-hour period following medication. However, the appropriate dose for a given patient may be difficult to determine due to variations in methadone metabolism which is affected by many factors. Early opioid withdrawal, requiring a higher dose of methadone, is often difficult to diagnose because many of the symptoms are also symptoms of other syndromes common in the methadone maintenance population. In this study, ten patients in stable methadone maintenance treatment reporting > or = 4 Himmelsbach signs of abstinence were compared with ten patients reporting fewer symptoms. Until recently, accurate, precise, and affordable determination of serum methadone level has not been readily available from commercial laboratories. This study has found that such measures are now available. Serum specimens from each subject were sent to three commercial laboratories for determination of serum methadone level. Results from the three laboratories were highly correlated. No statistical correlation was found between serum methadone level and number of Himmelsbach signs. Of the subjects reporting four or more symptoms, 40% had low serum methadone levels ( < 150 ng/ml); 60% did not. Of the subjects reporting fewer than four symptoms, 90% had serum methadone levels > or = 150 ng/ml. Subjects with > or = 4 Himmelsbach signs had lower dose-adjusted serum methadone levels, the amount of methadone circulating per mg dose, (t = 1.54, p < .0702). Thus, for patients who report symptoms which could be attributable to opioid withdrawal, measurement of serum methadone level may help to differentiate complaints due to early abstinence from those due to other medical conditions.