With advancing age, an increase in bone resorption relative to bone formation results in bone loss. Bone marrow stromal cells and their products support osteoclastogenesis from hematopoietic progenitors. Another of their products, osteoprotegerin (OPG), blocks the osteoclast-stimulatory effects of OPG ligand. We tested the hypothesis that with advancing age there is a decrease in OPG expression by human bone marrow cells. Bone marrow cells were obtained from 18 subjects (age range 38-84 years). Expression of mRNA transcripts of OPG was assessed by quantitative competitive RT-PCR. Median number of OPG transcripts in the younger group was 0.3 zetptomoles (range 0.01 to 1.30) and was higher than in the older group's median of 0.06 (range 0 to 0.5; p < 0.05). The decline in the expression of OPG with age may increase the capacity of stromal/osteoblast cells to support osteoclastogenesis.