To improve the response of parkinsonian patients to L-Dopa treatment, a new preparation of L-Dopa/benserazide with dual-release properties was developed. The breakable three-layer tablets with biphasic dissolution kinetics combine the advantages of the standard and sustained-release formulations. The clinical efficacy of this new formulation was assessed in an open-label, pilot study for 14 weeks conducted by Swiss neurologists. Sixty-one parkinsonian patients were included: 5 (8%) patients were de novo, 39 (64%) had fluctuations, and 17 (28%) without fluctuations. The mean Hoehn and Yahr stage was 2.6 and the mean duration of disease was 7.4 years. The best prestudy treatment was kept stable for 2 weeks before entering the first 8-week period in which standard and/or sustained L-Dopa treatment could be either entirely or partially substituted by the dual-release formulation, which was as far as possible kept unchanged during the second 6-week period. During the substitution period, the overall dose of L-Dopa was significantly increased by 11.5%, probably reflecting some differences in the bioavailability of the various galenical formulations, and the mean daily drug intakes were reduced from 5.4 at baseline to 4.1 at week 8 (a 24% reduction, p < 0.001). Sixteen percent of the patients dropped out of the study because of unsatisfactory results, but none left for safety reasons. At the end of the study, complete substitution was attained in 71% of the patients. The remaining 27% combined the dual-release formulation with standard and/or sustained-release L-Dopa. The efficacy of treatment was assessed with the Webster Score and qualified with a mean decrease of 27% (p < 0.001) between baseline and week 14. A significant decrease of the reported adverse events such as dyskinesias and end-of-dose or wearing-off akinesias was also observed before (27 patients, 44%) and after (9 patients, 17%) the substitution (p < 0.02). These results infer that the dual-release formulation is as good as or superior to any other galenic form of L-Dopa. In conclusion, the dual-release formulation of L-Dopa either introduced or substituted for the best treatment available showed good clinical efficacy and tolerability in all stages of the evolution of idiopathic Parkinson's disease treatment in this 14-week open-label study.