The reversibility of osteopenia secondary to isolated Ca deficiency (CaDef) is still not clear. We studied the effect of severe CaDef on Ca homeostasis and bone accrual in a ‘hypercalcaemic’ animal, the rabbit, during the post-weaning period and its reversibility on Ca supplementation. Male Belgian 5-week-old rabbit pups were fed CaDef diet (0·026% Ca) for 10 weeks. As compared with those fed with a normal chow diet (0·45% Ca), CaDef pups developed significant hypocalcaemia (P<0·05), hypocalciuria (urinary Ca 76 (sem 12) V 17 (sem 1) mg/l;P<0·005), hypophosphataemia (serum inorganic P 100 (sem 6) V. 65 (sem 4) mg/l; P<0·005), secondary hyperparathyroidism (SHPT) (serum intact parathyroid hormone human equivalent 18·2 (sem 1·4) V. 125·0 (sem 4·5) pg/ml; P<0·001) and elevated serum calcitriol levels (34·0 (sem 3·9) V. 91·0 (sem 1·0) pg/ml; v<0·005). Elevated urinary C-terminal telopeptide of class I collagen (P<0·005) and total serum alkaline phosphatase (P<0·005) suggested increased bone turnover. There was a significantly lower gain in bone mineral density (BMD) and bone mineral content (BMC) in the whole body and lumbar spine in vivo, and various sub-regions of the femur and tibia in vitro.Supplementation of adequate Ca (0·45% Ca) after 15 weeks on the normal diet resulted in rapid catch-up growth, and resolution of SHPT. Rapid gain in various BMD and BMC parameters continued at 30 weeks of age, and both were comparable with those in rabbits on a normal diet. We conclude that Ca deficiency-induced SHPT and poor bone accrual in growing rabbit pups are rapidly reversible with Ca supplementation. The present study indicates that early intervention may be a more appropriate window period for human nutritional corrective measures.