Gallium nitrate is biologically active in blocking bone resorption in vitro as well as in vivo. Administration of gallium nitrate to growing rats results in a dose-dependent accumulation of low levels of gallium in bone that is associated with specific changes in the mineral properties of bone. To elucidate in greater detail the changes induced by gallium, the properties of whole and density-fractionated bone samples from control and gallium-treated rats were examined. These studies showed that short-term treatment with gallium nitrate caused an increase in bone calcium and phosphate content. Devitalized bone powder from the gallium-treated rats was less soluble in acetate buffer and less readily resorbed by monocytes. Density fractionation analyses demonstrated that the largest proportion (76% by weight) of powdered metaphyseal bone particles from rats had a density of less than 2.15 g/cc. Following short-term treatment (14 days) with gallium nitrate (45 mg/kg body weight), a significant increase in the relative proportion of more dense bone (greater than or equal to 2.15 g/cc) was observed (24% for the control vs. 39% for the gallium-treated rats, P less than 0.01). In the diaphyseal samples, the largest proportion (88% by weight) of the bone powder had a density of greater than or equal to 2.15 g/cc. After short-term treatment with gallium, a slight decrease in mean diaphyseal particle density was observed. Measurement of calcium accretion with 45Ca in the gallium-treated rats demonstrated increased specific activity in the metaphyseal bone samples, densities = 2.0, 2.1, 2.15, and 2.25 g/cc; the difference was significant only for the 2.25 g/cc fraction.(ABSTRACT TRUNCATED AT 250 WORDS)