Lanreotide (LAN) 60 mg (LAN60), a new long-acting formulation of LAN alleged to suppress GH/IGF-I hypersecretion for 28 d in acromegalic patients, was administered in a prospective open multicenter study to 92 patients with active acromegaly (61 women and 31 men, aged 20-79 yr). LAN60 was given as adjuvant treatment (AT) in 62 patients; the other 30 patients [primary treatment (PT)] were de novo (n = 20) or previously treated only by pharmacotherapy (n = 10). After wash-out from previous treatments, LAN60 was started im every 28 d for 3 injections; the dose was then individually tailored, aiming at lowering GH to less than 2.5 micro g/liter and IGF-I to the normal range. After a median follow-up of 24 months (range, 6-48 months), IGF-I normalized in 65% of patients, decreasing from 199 +/- 8% (expressed as a percentage of the upper limit of normal range; mean +/- SE) to 87 +/- 4% (P < 0.0001). GH fell to less than 2.5 microg/liter in 63% of patients and to less than 1 microg/liter in 25%, decreasing from 20 +/- 3 to 3 +/- 0.4 microg/liter (P < 0.0001). A progressive increase in the rate of IGF-I normalization was observed (from 49% at 1 yr to 77% at 3 yr). The rate of GH/IGF-I normalization was 72% at 36 months by Kaplan-Meier analysis. No tachyphylaxis was observed throughout the study. Shortening the interval between injections to 21 d improved GH/IGF-I suppression. PT and AT patients achieved similar final GH/IGF-I levels and rates of normalization. Tumor shrank in 39% of assessable patients and in 50% of PT. Plasma glucose levels did not change, and high density lipoprotein cholesterol increased (by 19.3 +/- 5.1%; P = 0.0215). Gallstones appeared or worsened in 13% of patients. LAN60 is a new, very effective and long-lasting formulation for the treatment of acromegaly. The persistence of a powerful suppression of GH/IGF-I levels, the progressive increase in the rate of IGF-I normalization, and the similarity in the efficacy achieved in PT and AT patients point to a role for LAN60 in the primary treatment of acromegaly.