One difficulty for methadone maintenance treatment programs is the absence of a simple, analytical method useful for guiding adjustment of methadone dose. Currently, dose adjustment decisions are based upon: documentation of continuing opioid use by qualitative urine drug screens, patient complaints of dose not holding or physiological evidence of opioid withdrawal. Although decisions utilizing clinical parameters are helpful in adjustment of dose, a sizeable number of patients continue to receive inadequate doses. Incorrectly, many clinicians assume that low doses prevent toxicity and favor eventual abstinence. One solution to the question of efficacious dose adjustment would be utilization of repetitive blood sampling for monitoring plasma methadone concentrations to insure they remain within established therapeutic windows. Unfortunately, it is impractical to obtain ongoing blood samples from these patients because of poor venous access and the unpleasantness of frequent phlebotomy. To circumvent these problems, we developed analytical methods useful for estimating plasma methadone concentrations from random, spot urine samples. Over the past several years, we have analyzed approximately 16,000 samples (urine plus plasma) drawn from 200 methadone maintenance patients. These data have allowed generation of methadone dose vs. plasma methadone concentration curves, demonstrating why dose adjustment decisions should be buttressed with objective laboratory data. In addition, these methods are useful for uncovering covert methadone supplementation and diversion. These improvements in clinical care have been accomplished using a computerized, pharmacokinetics program which accounts for compounding effects of urine pH, specific gravity, volume of distribution and gender upon renal methadone excretion. The program allows calculation of total plasma methadone concentrations from concurrent urine measurements, which are within 5-10% of actually measured values. This system has eliminated the need for venous blood sampling, resulted in optimization of patient doses and helped uncover supplementing or diverting of methadone.