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Objective. To evaluate the effect of early range-of-motion intervention on bone strength and bone turnover in very low birth weight infants. Methods. Twenty-four infants (mean birth weight: 1135 [+ or -] 247 g; mean gestational age: 28.5 [+ or -] 2.3 weeks) were matched for gestational age and birth weight and then randomly assigned into exercise (n = 12) and control (n = 12) groups. Exercise protocol started at the first week of life and involved daily extension and flexion range of motion against passive resistance of the upper and lower extremities (5 minutes per day, 5 days per week, 4 weeks). Growth parameters, bone strength, and biochemical markers of bone homeostasis were measured at enrollment and after 4 weeks. Bone strength was determined using quantitative ultrasound measurement of bone speed of sound (SOS) at the middle left tibial shaft. Results. Bone SOS decreased significantly in the control group during the study period (from 2892 [+ or -] 30 m/sec to 2799 [+ or -] 26), whereas bone SOS of the exercise group remained stable (2825 [+ or -] 32 m/sec and 2827 [+ or -] 26 m/sec at baseline and 4 weeks, respectively). This significant difference in bone SOS was not expressed in the biochemical markers of bone homeostasis. Conclusions. There is a significant postnatal decrease in the bone SOS of very low birth weight infants. A brief range-of-motion exercise attenuates the decrease in bone strength and may decrease the risk of osteopenia. Pediatrics 2003;112:15-19; premature, osteopenia, exercise, quantitative ultrasound, speed of sound., ABBREVIATIONS. VLBW, very low birth weight; DEXA, dual-energy x-ray absorptiometry; QUS, quantitative ultrasound; SOS, speed of sound; BSAP, bone-specific alkaline phosphate; ICTP, carboxy terminal cross-links telopeptide of type-I collagen; CV, [...]