The effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDPTM) on bone mineral metabolism was tested in 4 healthy young men during 20 weeks of continuous bed rest. Two subjects received an oral dose of 5 mg/kg/day and the other 2 20 mg/kg/day. The low dose had two minor effects: the increase in bone accretion rate which usually occurs during bed rest was prevented, and there was an accentuation of the bed rest induced increase in hydroxyproline excretion. Skeletal mineral loss, assessed by calcium balance measurements and gamma ray absorptiometry of the calcaneus, occurred at the rate previously noted in untreated control subjects. Two types of drug effect were apparent at the higher dosage: one was immediate and sustained--a rise in serum phosphorus concentration and a fall in serum alkaline phosphatase activity. The other was delayed and progressive--a decline in urinary hydroxyproline excretion and in the rates of bone accretion and resorption. Skeletal mineral loss may have been affected; the usual negative mineral balance developed during the first half of the study, then disappeared during the last few weeks. However, gamma ray absorptiometry revealed no attenuation of the calcaneal mineral losses.