Osteoclasts were harvested from explants of five patients with premature unilateral coronal synostosis and plated on devitalized bovine bone wafers. The planar surface areas of resorption lacunae were quantitated by means of light microscopy and a digital imaging system. Osteoclasts isolated from involved regions of premature synostosis exhibited enhanced resorption when compared with osteoclasts isolated from noninvolved cranial bone in the same patients (p < 0.05). When the involved osteoclasts were exposed to conditioned media from non-involved osteoblasts, the in vitro metabolism was reduced consistent with noninvolved osteoclasts. The results suggest there may be a primary cellular defect and that there appears to be a complex coupling between osteoblast and osteoclast function that may lead to sutural synostosis.