Almost all patients with idiopathic Parkinson's disease respond to levodopa and progress steadily, requiring an increased overall dosage with time. Sinemet CR4 offers a theoretically attractive method of achieving gradual sustained release of levodopa over time which may be more physiological to striatal dopamine receptors in the early stages of the disease. This study evaluated 20 patients with moderate to severe Parkinson's disease who were treated with Sinemet CR4 over a 1-year period. Eleven patients completed the full year on therapy, and nine subjects withdrew. Of the withdrawals, two subjects died from non-Parkinson's disease-related illness, three showed no therapeutic benefit, and four responded well for a minimal 6-month period, but then lost therapeutic benefit and developed more severe dystonias. A higher overall levodopa dosage was required by all patients, and side-effects of levodopa were still present in most patients. However, the nocturnal benefit of this long-acting preparation was observed by all the patients in the study. Slow onset of action of Sinemet CR4 resulted in early-morning immobility. Sinemet CR4 cannot replace standard Sinemet, but appears to be a useful form of adjunct therapy in selected patients.