Acromegaly is associated with increased morbidity and mortality. Surgery, radiotherapy (RT) and medical therapy are the treatment options to decrease GH and IGF-I concentrations to levels associated with cure or normalisation of mortality. We examined the response to dopamine agonists (DA) and somatostatin analogues (SSA) in 276 patients with acromegaly who received medical therapy during follow up (198 DA, 143 SSA). One hundred and seventy two had surgery and 73 RT prior to medical therapy. GH and IGF-I values before and 12 months after initiation of therapy were analysed. In the DA group basal prolactin levels did not predict response to therapy (median GH% reduction): hyperprolactinaemia 26.7% (10.448) vs normal prolactin 34.8% (0.253.2), P=0.58. Prior surgery was associated with a less marked GH% (P=0.026) and IGF-I% reduction (P=0.0043): surgery group 23.9% (−9.948.5) and 9.2% (−1.026.6), no surgery group 40.5% (1571) and 40% (15.488.2). Prior RT was associated with an enhanced GH% reduction but no significant effect on IGF-I% reduction: no RT (GH 20.5% (−9.939.1), IGF-I 9.4% (−16.228.7)) vs RT (GH 50.8% (15.567.5, P=0.0029), IGF-I 22.2% (3.157.9 P=0.07)). In the SSA group there was no effect of prior surgery on %GH or IGF-I decrease, P=0.63 and 0.78, respectively. Prior RT did not have an effect on decrease in GH (P=0.77) but it lead to a lower IGF-I% reduction (P=0.045). The role of pituitary hormone deficiency in the response was assessed; no differences were found if there was ACTH or TSH deficiency. However in the DA group, gonadotrophin deficiency was associated with less marked decrease in IGF-I% (4.5 (−0.3611.52) vs 25 (9.440.4), (P=0.04)). The efficacy of DA in patients with acromegaly is irrespective of basal prolactin levels. Prior surgery and radiotherapy are associated with differences in GH and IGF-I response to DA and SSA. However ACTH and TSH deficiency did not have an influence in the response.