Recent studies indicate that the bisphosphonate pamidronate reduces skeletal complications caused by tumor osteolysis. In this investigation, the cellular mechanism through which pamidronate affects tumor‐induced osteoclastogenesis is studied in osteopetrotic mice. A unique animal model is employed which studies the effect of pamidronate on a tumor (2472 sarcoma) which induces osteoclastogenesis in osteoclast‐deficient mice (oplop). This model provides opportunity to specifically study effects on osteoclast formation and findings suggest that pamidronate decreases the number of osteoclasts at sites of 2472 tumor by decreasing the number of osteoclast precursor cells at the level of myeloid precursors. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.