Although growth hormone (GH) concentrations are not always pathologically elevated in patients with acromegaly, it has been suggested that the metabolic and somatic consequences of this condition may be due to a loss of the normal episodic secretion of GH. To examine the effects of maintaining modest but constant levels of circulating GH, we administered continuous subcutaneous infusions of growth hormone (CSIGH) to eight previously untreated GH-deficient children (6-19 yr). CSIGH given for 90 h in doses equivalent to the standard dose for replacement therapy, raised mean serum GH levels from less than 3.0 to 5.9 ± 1 .0 ng/ml. In comparison, 24-h mean GH levels in five normal adolescents averaged 10.1 ± 1.5 ng/ml. As expected, however, normals showed much more variability in GH concentration. The constant elevations in serum GH levels achieved with CSIGH produced significant impairment of oral glucose tolerance. During CSIGH, plasma glucose concentrations 60-120 min after oral glucose loading were 30-40 mg/dl higher than corresponding pre-infusion values (P< 0.01). This impairment of oral glucose tolerance during CSIGH occurred despite a doubling of the area under the insulin/time curve after oral glucose (P< 0.02 versus pre-infusion area). Indeed, plasma insulin levels after oral glucose in patients on CSIGH exceeded those observed in normal controls, suggesting that CSIGH,had induced a degree of insulin resistance. There was a transient increase in plasma free fatty acid levels on the first day of CSIGH. Somatomedin-C concentration remained unchanged in four of six patients. We conclude that small but sustained increases in growth hormone concentrations in GH deficiency can, when infused continuously, have effects on fuel metabolism similar to those observed during pathologic GH hypersecretion.