The effect of a schedule of three daily injections of 100 μg octreotide (pen treatment) compared with that of a continuous sc infusion of 300 μg/24 h on GH and IGF-I suppression, and other GH-dependent parameters was studied in 10 acromegalic patients in a cross-over study. Treatment was administered via a specially designed pen or a pump for 4 weeks. Following a washout period of a further 4 weeks, patients were switched to the other mode of delivery. Mean GH levels decreased from 26.2±4.7 to 9.9±3.1 mU/l (p=0.007) during pen therapy and to 7.7±2.4 mU/l (p=0.003) during pump treatment. IGF-I levels decreased from 75.6±9.5 to 42.0±9.3 nmol/l (p=0.003) during pen treatment and to 32.5±2.5 nmol/l (p=0.001) during pump treatment. There was a significant difference in IGF-I levels between pen and pump treatments (p=0.03). In 7 patients the IGF-I levels normalized during pump treatment compared with 3 patients in the pen treatment group. There was no change in the free T4 index levels, but the free T3 index significantly decreased during therapy, without changes in plasma TSH. This study demonstrates that continuous infusion with octreotide results in a better control of GH oversecretion than the intermittent mode of delivery.