OBJECTIVE Until now, GH treatment in GH-deficient adults has employed dose schedules of GH based on body weight or body surface area and has ignored individual responsiveness to GH. This trial has studied the effects of an individualized GH dose adjusted to match a combination of clinical response, normalization of serum IGF-I concentration and body composition. METHODS Two closely-matched groups, each comprising 30 GH-deficient adults, 38 men and 22 women aged 48 years, were treated with GH for 12 months. The high dose (HD) group received a target dose of 12 micrograms/kg per day and the individualized dose (ID) group received an initial daily GH dose of 0.17 or 0.33 mg per day (0.5 and 1 IU, respectively), independent of body weight, with dose adjustments thereafter. METHODS Serum concentrations of IGF-I, lipoprotein(a), insulin, calcium, intact PTH, osteocalcin and blood glucose were measured. Body composition was determined according to a 4-compartment model using total body potassium and tritiated water as input variables. Total body nitrogen was measured by in vivo neutron activation and total body bone mineral content by dual energy X-ray absorptiometry. RESULTS At 12 months, the daily dose of GH was 0.55 +/- 0.03 mg and 0.45 +/- 0.03 mg in the HD and ID groups, respectively (P < 0.05). In the HD group, the mean serum IGF-I increased to levels well above the predicted level, while in the ID group the mean serum IGF-I normalized. Side-effects were experienced by 70% of the subjects in the HD group and by 30% in the ID group (P < 0.001). A similar response to GH in terms of body composition, glucose homeostasis, lipoprotein(a) and blood pressure was obtained in both treatment groups. However, the treatment response in terms of serum calcium, intact PTH and osteocalcin was more marked in the HD group. CONCLUSIONS Similar efficacy, with a lower dose of GH and fewer side-effects, was obtained by considering individual responsiveness to GH as compared to higher doses of GH adjusted to match body weight.