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We tested the effect of co-treatment of acromegaly with a somatostatin analogue (SA) and a growth hormone receptor antagonist (GHA). Eleven patients underwent: 1) conventional treatment with SA, 2) discontinued treatment, 3) 6 weeks treatment with GHA (10 mg), 4) 6 weeks treatment with GHA (15 mg), 5) 3 months combined SA and GHA. Circulating IGF-I was lowered by GHA and more so with combined treatment. Treatment with GHA increased endogenous GH levels, which was partly reversed by combined treatment. Plasma glucose levels were highest during SA treatment and lowest with GHA. Co-treatment of acromegaly with SA and GHA is a promising concept.