The diphosphonates are a group of synthetic compounds which are adsorbed onto hydroxyapatite crystal surfaces and inhibit both the growth and dissolution of these crystals. They also inhibit mineralisation and resorption of bone in vivo. The effects of diphosphonates were tested on the attachment of macrophages to bone and on the dissolution of bone mineral by macrophages. Attachment was unaffected but resorption was inhibited. Diphosphonates were found to be cytotoxic at much lower concentrations when bone mineral was present, and the most likely explanation for the effects of diphosphonate on bone resorption is that the drug is adsorbed onto the mineral surface where it reaches cytotoxic concentrations.