Baclofen is a centrally acting muscle relaxant used for treatment of spasticity. Some patients, to experience adequate symptomatic relief, require dosages of baclofen that significantly exceed the conventional 80 mg daily maximum advocated by the 1992 Physicians' Desk Reference. In this pilot study of baclofen kinetics and dynamics in eleven patients, the safety and efficacy of high dose baclofen was confirmed. The data suggest that the pharmacokinetics of high dose baclofen may vary from those described previously. Time-to-peak plasma levels and plasma half-lives were noted to be substantially longer than prior reports indicate. Baclofen blood levels were observed to rise gradually over time in some patients on a stable dosing regimen, probably a result of impaired renal clearance. These findings may indicate that a change in pattern of prescription is warranted and that a reliable and practical measurement of systemic baclofen levels has a useful role in clinical practice, particularly for the patient with neurogenic bladder and potential renal insufficiency.