Bone density in growth hormone (GH) deficient children is decreased more than expected for delayed skeletal maturation. Previous studies suggest GH enhances mineral retention and deposition in bone. Seven GH deficient prepubertal children were studied during 2 years of GH therapy to assess the effect on bone density and plasma osteocalcin. Bone density (radiographic photodensitometry) of the phalanges (cortical and trabecular bone) was expressed as the standard deviation score (SDS) of the mean for sex, bone age and chronological age. Relative osteopenia, less pronounced for bone density/bone age (BD/BA) than bone density/chronological age (BD/CA), improved significantly during GH therapy. After 12 months there was increase over pretreatment levels, significant for BD/CA (-1.65 +/- 0.46 vs -1.15 +/- 0.64; mean +/- SD: p = 0.002), but less pronounced for BD/BA. After 24 months increase in both measurements continued, reaching significance also for BD/BA (Pre: -1.02 +/- 0.55 vs -0.41 +/- 0.29; p = 0.011). Plasma osteocalcin levels were low before GH therapy (11.6 +/- 9.9 ng/ml; n = 7; vs control 24.4 +/- 12.5 ng/ml; n = 21; p < 0.05), rose significantly after one week (31.2 +/- 10.5 ng/ml; p < 0.001), with continued upward trend to plateau between 2-6 months, with elevated levels persisting during 2 years of GH therapy. CONCLUSIONS The early and sustained rise in plasma osteocalcin and subsequent increase in bone density with continued gain over 24 months of the study suggests that GH therapy in GH deficient children has a significant prolonged effect on bone formation and mineralization in addition to stimulating linear growth.