Osteoclasts have been defined as calcitonin (CT) and vitronectin (VN) receptor (R) positive, and CD14-, CD11b- and CD11c-negative cells which resorb bone. The aim of this study was to identify the phenotype of the osteoclast precursor. Osteoclasts were generated by co-culturing peripheral blood mononuclear cells (PBMNCS) with the rat osteoblastic UMR 106 cell line. On days 2-4 at least 80% of CTR-positive cells co-expressed CD14, CD11b and CD11c (monocyte markers), but by day 14 < 3.3% expressed these markers. Selection of CD14-positive monocytes from PBMNCS enhanced osteoclastic bone resorption 2-4-fold compared to unfractionated PBMNCS. This study demonstrates that osteoclasts derive largely from CD14-positive monocytes.