We performed fetal nigral transplantations in 4 Parkinson's disease (PD) patients. Solid grafts were bilaterally implanted into the postcommissural putamen using 3 to 4 donors per side aged 6 1/2 to 9 weeks postconception. Transplant deposits were separated by no more than 5 mm in three dimensions. Cyclosporine was employed for a total of 6 months. Patients were evaluated at baseline and at 1, 3, and 6 months postoperatively. Striatal 18-fluorodopa uptake was assessed by positron emission tomography at baseline and at 6 months postoperatively. The procedure was well tolerated in all patients. One patient had a clinically asymptomatic superficial cortical hemorrhage along the needle tract and a second had transient postoperative confusion and hallucinations. All patients experienced clinically meaningful benefit. Significant improvement (p < 0.05) was detected in total UPDRS score during the "off" state, Schwab-England disability score during the "off" state, percent "off" time, and percent "on" time with dyskinesia. Increased striatal fluorodopa uptake was observed bilaterally in each patient, with mean increases of 53% on the right (p = 0.01) and 33% on the left (p = 0.08). Our study demonstrated clear and consistent improvement in clinical features and striatal fluorodopa uptake following fetal tissue transplantation in patients with advanced PD whose condition was not improved preoperatively by drug manipulation. These preliminary results are encouraging and support further studies to evaluate grafting strategies as a therapy for PD.