The efficacy of dopaminergic agents in the medical treatment of pituitary adenomas is well known. Quinagolide is a nonergot derivative dopamine agonist, which binds dopamine D-2 receptors with high affinity. The treatment with this drug is reported to suppress hormone levels and to cause tumor shrinkage in prolactinomas and in a few GK-secreting pituitary adenomas. In clinically nonfunctioning pituitary adenomas (NFPA), the efficacy of quinagolide treatment is controversial. The scintigraphy of the pituitary region using I-123-methoxybenzamide (I-123-IBZM) allows US to visualize in vivo the expression of dopamine D-2 receptors on pituitary tumors. In this study, the pituitary scintigraphy with I-123-IBZM was performed in 14 patients with macroadenoma before starting a long-term treatment with quinagolide: 6 NFPA with high circulating alpha-subunit levels, 4 PRL-secreting, and 4 GH-secreting adenomas. A 3-point score was used to grade the ligand accumulation within the pituitary adenomas: 0 = negative, 1 = moderate uptake (equal to that recorded in the cerebral cortex), and 2 = intense uptake (equal to that recorded in the basal nuclei). The treatment with quinagolide was carried out at the dose of 0.3-0.6 mg/day for 6-12 months. Clinical, biochemical and hormonal assessment was repeated monthly during the first 3 months, then quarterly. Sellar magnetic resonance imaging was performed before and after 6 and 12 months of quinagolide treatment, to evaluate tumor shrinkage (>25% of baseline size). In all 14 patients, a significant positive correlation was found between the degree of I-123-IBZM uptake and the clinical response to quinagolide treatment (r = 0.90; P < 0.001). In particular, the normalization of serum alpha-subunit and PRL levels, respectively, was achieved in 3 patients with NFPA and in 2 patients with prolactinoma, who showed intense I-123-IBZM uptake in the pituitary region. In 4 of these 5 patients with positive scan, a significant tumor shrinkage occurred between 6 and 12 months after the beginning of quinagolide treatment. In all patients with GH-secreting adenoma, no significant uptake of I-123-IBZM was found and no significant decrease of circulating GH and/or insulin-like growth factor-I levels, and tumor shrinkage was obtained during long-term treatment with quinagolide. In conclusion, the pituitary scintigraphy with I-123-IBZM can be considered a useful tool to indicate adenomas with significant expression of functioning D-2 receptors. This innovative technique may predict the response to long-term treatment with quinagolide in patients with NFPA, where the lack of pituitary hormone hypersecretion makes difficult the monitoring of medical treatment efficacy.