There is increasing awareness that growth hormone (GH) replacement therapy is also essential in adult patients with growth hormone deficiency (GHD). There are little data available on the dose requirements for replacement therapy in this age group. In childhood, the growth response to GH therapy can serve as an indicator for the correct replacement dose. Because this indicator does not exist in adults, we analyzed growth factors and biochemical markers of bone metabolism by specific radioimmunoassays in a group (n = 12) of adult patients (age, 20.0-31.6 years) with GHD with childhood onset before and after a 4-week treatment period (daily, s.c.) with recombinant, human GH at different doses (0.125, 0.25 and 0.5 IU/kg body weight/week). Comparing the basal levels to those on low-dose GH (0.125 IU/kg/week) and on a high dose (0.5 IU/kg/week), the following results were obtained. Insulin-like growth factor-I (IGF-1) in serum: basal, 68.6 ± 37 ng/ml; low dose, 176.9 ± 65 ng/ml (p ≤ 0.05); high dose, 380.6 ± 200 ng/ml (p < 0.01). IGF-binding protein-3 in serum: basal, 2.13 ± 0.58 mg/l; low dose, 3.23 ± 0.84 mg/l (p < 0.01); high dose, 3.97 ± 0.82 mg/l. Osteocalcin in serum: basal, 3.88 ± 1.27 ng/ml; low dose, 7.01 ± 2.20 ng/ml (p < 0.01); no further increase. Procollagen-I peptide in serum: basal, 113.6 ± 36.7 μg/l; low dose, 211.6 ± 90.4 μg/l (p < 0.01); no further increase. Galactosylhydroxylysine excretion in urine: basal, 12.9 ± 5.24 μmol/g; low dose, 23.3 ± 13.2μmol/g(p < 0.05); high dose, 27.7 ± 13.7 μmol/g. We conclude that the parameters measured possibly represent a useful tool for the assessment of the correct replacement dose in adult GHD. As the lowest dose investigated (0.125 IU/kg body weight/week) normalized serum levels of growth factors and parameters of bone metabolism, this dose might be the advisable replacement dose in adult GHD.