Pegvisomant monotherapy once daily returns concentrations of insulin-like growth factor I (IGF-I) to normal in most patients with acromegaly, but is very costly. In a 42-week dose-finding study, we assessed the efficacy of the combination of long-acting somatostatin analogues once monthly and pegvisomant once weekly in 26 patients with active acromegaly. Dose of pegvisomant was increased until IGF-I concentration became normal or until a weekly dose of 80 mg was reached. IGF-I reached normal concentrations in 18 of 19 (95%) patients who completed 42 weeks of treatment, with a median weekly dose of 60 mg pegvisomant (range 40-80). No signs of pituitary tumour growth were noted, but mild increases in liver enzymes were observed in ten patients (38%). This combined treatment is effective, might increase compliance, and could greatly reduce the costs of medical treatment for acromegaly in some patients.