Bone turnover in T-cell deficient mice was investigated by comparing parameters of bone physiology in athymic (nude) and euthymic mice. Static and dynamic bone histomorphometry, serum biochemical assays, body weight and tibia length measurements, and bone ash determination were completed in 6- and 12-wk-old athymic (nude) mice (NIH: Swiss nu/nu) and euthymic mice (nu/+) (10 mice/group). In vitro bone resorbing activity stimulated by parathyroid hormone (PTH) or prostaglandin E₂ (PGE₂) was measured in calvaria of neonatal athymic and euthymic mice. Athymic mice had smaller vertebral tissue area (p < 0.01), tibia length (p < 0.001), and less body weight (p < 0.01) than euthymic mice. The percent double labeled surface (p < 0.05) and mineralizing perimeter (p < 0.01) were reduced in athymic as compared to age-matched euthymic mice. Osteoclast number was reduced in the 6-wk athymic mice as compared to 6-wk euthymic mice. Osteoclastic perimeter was reduced in the 12-wk-old mice (athymic and euthymic) as compared to the 6-wk-old mice. Serum calcium was lower at both ages in athymic mice (p < 0.01) as compared to euthymic mice. Serum alkaline phosphatase levels were reduced (p < 0.01) in 12-wk-old athymic mice as compared to age-matched euthymic mice, and were greater in 6-wk-old mice than 12-wkold mice. Athymic mice had greater femur density than euthymic mice (p < 0.01), and lower (p < 0.001) percent ash weight of dry bone compared to euthymic mice. There was no difference in bone resorbing activity in vitro stimulated by PTH or PGE₂ between athymic and euthymic mouse calvaria. These data indicate that: (a) bone turnover is reduced during skeletal maturation (12- compared to 6-wks) in mice, (b) athymic mice had reduced organ-level bone size and decreased percent ash weight compared to euthymic mice, (c) athymic mice had decreased mineralizing perimeter compared to euthymic mice, and (d) tissue-level bone turnover was not markedly altered in athymic mice.