Controlled-release carbidopa/levodopa 50/200 (Sinemet CR) and standard carbidopa/levodopa (Sinemet 25/100) were compared in a multicenter double-blind trial involving 202 patients with advanced Parkinson's disease and motor response fluctuations. Treatment with Sinemet CR significantly reduced daily "off" time. According to both physician and patient global ratings, patients showed significant improvements with Sinemet CR compared to treatment with standard Sinemet. Patients preferred Sinemet CR treatment by a ratio of approximately 2 to 1. Daily dosing frequency was 33% less with Sinemet CR, while daily intake of levodopa required was increased by 25%. The safety profiles of the 2 formulations were similar. We conclude that Sinemet CR is superior to standard Sinemet for many patients with advanced Parkinson's disease, although it does not solve the problem of fluctuating motor performance.