The aim of this study was to evaluate the efficacy of a 6-month treatment with lanreotide (LAN) (60-90 mg/month) alone and combined with cabergoline (CAB) (1.5-3 mg/week) in 10 acromegalic patients previously demonstrated to be poor responders to octreotide (OCT) (0.6 mg/day) alone and combined with quinagolide (CV) (0.6 mg/day). All patients had previously undergone unsuccessful surgery and none of them received radiotherapy. Immunohistochemistry showed intense positive GH staining in all adenomas, positive PRL staining in 5 adenomas and faint ACTH or FSH/LH positive staining in other 2 adenomas. Moderately elevated serum PRL levels (35 and 47 ng/ml) were recorded in two patients. Fasting plasma IGF-I and serum GH levels were assayed at baseline and 30, 60, 90 and 120 days after each treatment. Gallbladder ultrasonography and sellar MRI were performed before and after 6 months of OCT and LAN treatments. After OCT treatment circulating GH and IGF-I levels remained elevated in all patients, while after 3 months of combined OCT + CV treatment, serum GH levels were suppressed (below 2.5 ng/ml) in only 1 patient. Significant increase of the percent GH (83.9 +/- 4.3 vs. 70.3 +/- 5.6%, p < 0.01) and IGF-I suppression (54 +/- 4.4 vs. 45.3 +/- 5.7, p < 0.01) and decrease of the nadir of GH (8.5 +/- 1.2 vs. 14.6 +/- 1.9 ng/ml, p < 0.01) and IGF-I (400.9 +/- 32.8 vs. 462.1 +/- 45.1 ng/ml) were obtained with the combined treatment when compared to OCT treatment alone. After a 15-30 days wash-out, circulating GH and IGF-I levels significantly increased up to pretreatment level in all patients. After 6 months of treatment with LAN, suppression of serum GH was achieved in 1 patient, but no difference in GH (66.3 +/- 6.3%) and IGF-I (43.9 +/- 4.6%) suppression was recorded in comparison to OCT treatment. After 3 months of treatment with LAN combined with CAB, suppression of serum GH and normalization of plasma IGF-I levels was achieved in 4 and 5 patients, respectively. Percent suppression of GH (88.1 +/- 2.1%) and IGF-I (57.5 +/- 2.8%) was significantly greater with the combined treatment than with LAN treatment alone. In the 7 patients with evident residual mass no change was documented by magnetic resonance imaging (MRI). None of the patients withdrew LAN + CAB treatment for poor tolerance, one patient had mild hypotension. Sludge was shown after 6 months of LAN treatment in one patient without notable change after 3 months of LAN + CAB treatment. In conclusion, the treatment with dopaminergic drugs such as CV and CAB, significantly increased the efficacy of somatostatin analogs, and can be used in combined therapy in poorly responsive patients.