Good clinical results of unreamed nailing have been observed primarily in cases of open fracture. However, it is still unclear whether unreamed nailing is a suitable procedure for fractures that have previously been treated with reamed nailing. Since histological findings on bone healing after unreamed nailing were not available, an animal experiment on sheep was undertaken. The aim was to investigate whether there were differences in the nature of bone healing following reamed and unreamed nailing procedures. Fluorescence microscopy clearly showed that maximal callus formation occurred within 4 weeks after unreamed nailing and within 6 weeks after reamed nailing. Callus formation was also more prolific after unreamed than after reamed nailing. It was demonstrated by microradiography that bone regeneration progressed more rapidly, in terms of both periosteal and interfragmentary callus, after unreamed nailing. No disturbances of bone healing and no greater risk of pseudarthrosis were observed following unreamed nailing. Histological investigations showed that bone healing was faster after unreamed nailing and there was a reduced loss of vitality. This is of particular clinical relevance in the surgical treatment of fractures with severe soft tissue injury and of open and comminuted fractures. These results indicate that an extension of the indications for unreamed nailing should be considered.