Serum osteocalcin and bone alkaline phosphatase (BAP) were measured in samples drawn at 8 a.m. in 7 patients with GH deficiency treated with recombinant human growth hormone (rhGH) (2 IU/day subcutaneously at 8 p.m.), and 7 normal controls. Patients treated with 2 IU/day had lower BAP than controls (P less than 0.05). Further, increasing doses of rhGH were given subcutaneously to each of the 7 patients for 3 consecutive 14-day periods (2, 4, and 6 IU/day at 8 p.m.) followed by 14 days off treatment. At the end of each period, the patient was hospitalized for frequent blood sampling from 8 p.m. to 11 a.m. the following day. A dose-dependent increase in area under the curve (AUC) was seen for osteocalcin (P less than 0.05), whereas the increase in AUC for BAP just failed to reach significance (P less than 0.10). The nocturnal pattern of serum osteocalcin in patients on 4 and 6 IU/day were statistically indistinguishable from those in controls. During treatment with 2 IU/day and the off-treatment period, the pattern was significantly different from controls (P less than 0.05). In conclusion, rhGH has a dose-dependent effect on basal osteoblastic activity and the nocturnal pattern of osteocalcin. Serum osteocalcin increases within hours following rhGH administration. However, 2 IU/day is inadequate to maintain normal levels and nocturnal variation in markers of osteoblastic activity.