There are few long-term studies of cabergoline (CAB) administration in patients with macroprolactinomas. All of these studies included different type of patients, such as patients with idiopathic hyperprolactinemia, microprolactinomas and previously treated or untreated macroprolactinomas. We report a study of CAB treatment conducted exclusively in patients with newly diagnosed, untreated, macroprolactinomas. Twelve patients (6 M, 6 F) with macropolactinomas were investigated prospectively for 12 months to determine the effects of prolonged treatment with CAB on serum PRL levels, tumor size, visual fields and prevalence of side effects. Nine of these patients continued therapy and follow-up for 6 or more additional months of CAB administration. Our results demonstrated that CAB decreased the volume of the tumor in all patients investigated 3 months after the initiation of treatment. Specifically, mean tumor volume was 11,327 +/- 25,187 mm3 before the study and decreased to 4281 +/- 8465 mm3 and 1544 +/- 2118 mm3 in the second and last measurement, respectively. However, these changes were not statistically significant, most probably due to the very high SD. As far as the maximum diameter is concerned, mean values was 22.8 +/- 16.9 mm before the study and decreased to 16.6 +/- 10.9 mm and 13.4 +/- 7.5 mm in the 3 months and last examination, respectively. These changes were statistically significant (p = 0.005 and p = 0.007). The mean percentage decrease of the tumor volume and maximum tumor diameter was 42.4 +/- 14.0% and 24.7 +/- 4.8% respectively in the third month and 67.2 +/- 17.3% and 35.9 +/- 11.8% in the last estimation. These differences were statistically significant, (p < 0.01 and p < 0.001, respectively). The same was also true for PRL levels, the mean of which was 14,719 +/- 20,616 before treatment and became normal in the third month (153.3 +/- 63.4) and continued to be throughout the study. Four patients had visual field defects, which improved or even completely resolved during the treatment period. Finally, the CAB doses used were particularly small, i.e., 0.5-2 mg per week. All the patients recovered from their clinical problems and symptoms. This remarkable improvement was associated with an excellent tolerability of the long-term treatment due to the low incidence of side effects. In conclusion, the results of the present study demonstrated that CAB produced tumor shrinkage and normalized PRL levels in all the patients studied. Also, clinical symptoms disappeared and visual fields improved. These beneficial effects were associated with a very high compliance rate and minimal side effects. Thus, CAB can be considered a first-line pharmacological treatment of macroprolactinomas.