The effects of gallium nitrate (GN) were evaluated on osteopenia induced by ovariectomy (OVX) and a low-calcium diet (LCD) in Sprague-Dawley rats. Twenty-five rats (300-400 g) were randomized into four groups of 5-7 animals: (I) OVX LCD treated with GN for 22 weeks; (II) OVX LCD treated with GN for 10 weeks; (III) OVX LCD treated with saline; and (IV) sham-operated (SO), normal diet, treated with saline. GN-treated rats received a 30-mg/kg subcutaneous single dose of elemental gallium, followed by 10 mg/kg per week, whereas control animals received an equal volume of saline. All animals were euthanized at 22 weeks. Measurements of bone density and histomorphometry, performed on the proximal portion of the tibia, indicated significant bone loss in all OVX LCD animals. GN-treated rats in group I gained significantly less weight than those in the other groups, and their blood urea nitrogen increased, suggesting a nephrotoxic effect. After discontinuation of GN, rats in group II gained weight at the same rate as those which had received only saline. Bone formation rates in the GN-treated rats were double those of the saline-treated OVX animals and more than 10 times those of SO controls. Although the bone formation rate in GN-treated rats increased, GN had no effect in preventing the loss of bone surface, density and volume induced by OVX LCD. These findings suggest that although GN may enhance osteoblastic activity, this agent alone does not appear effective in the prevention of bone loss induced by OVX LCD.