In five levodopa (L-dopa)-treated patients with Parkinson's disease with severe fluctuations of motor performance, plasma L-dopa as well as dopamine levels were measured during 2 days, first under optimal standard L-dopa with peripheral decarboxylase inhibitor (PDI) and then after a dose adjustment period using slow-release L-dopa/benserazide (Madopar HBS) in an open inpatient trial. Three patients benefited from the slow-release preparation; two patients deteriorated with a tendency to have an unpredictable response, a delay to turn "on" with the first dose in the morning, as well as an increase in dyskinesia corresponding to L-dopa cumulation during the day. These problems were subsequently also seen during the follow-up period of 1 year in those patients who benefited from Madopar HBS as inpatients. This might indicate that patient compliance is more difficult with the new formulation. After 1 year all patients had returned to their previous standard L-dopa/PDI treatment. L-Dopa levels continued to fluctuate, but to a lesser degree with Madopar HBS. The equivalent L-dopa dosage had to be increased by 56% (29-100%) with Madopar HBS while mean dopamine levels increased in four patients (by 47-257%) without the occurrence of peripheral side-effects. This implies that with the new formulation more L-dopa is metabolized to dopamine and explains the necessity to increase the equivalent L-dopa dosage.