We investigated the potential of [(11)C]acetate positron emission tomography (PET) to detect local recurrence in prostate cancer (PCA) in patients with increasing PSA following complete prostatectomy. A total of 31 patients were studied and compared with the results of transrectal ultrasound (TRUS) combined with biopsy and clinical follow-up. Whole-body PET scan was performed 5 min after injection of 0.8 GBq [(11)C]acetate and completed within 1 h. Focally increased tracer uptake below the urinary bladder or in an abdominal lymph node region was considered as relapse. TRUS followed by biopsy verified recurrence in 18 patients and ruled it out in 13 patients. PET demonstrated local recurrence in 15 out of the aforementioned 18 patients. PET also demonstrated distant lymph node involvement and bone metastases in five patients each. No focal [(11)C]acetate uptake was demonstrated in the prostate bed in patients with negative biopsy. These patients had no evidence of disease during 6 months of follow-up. In the subgroup of patients with PSA <2.0 ng/ml ( n=8), five patients had positive PET findings, with four of them verified by biopsy. It is concluded that [(11)C]acetate PET is a promising new tool for the diagnosis of PCA recurrence and can influence patient management.