Biological studies of two titanium dioxide polymorphs, rutile and anatase, have produced conflicting results. Generally, the in vivo and in vitro methods used to evaluate pneumoconiotic dusts have shown the polymorphs to be inert, but occasionally both minerals have been reported to produce effects consistent with biologically active minerals. Many of these reports failed to specify which polymorph was used experimentally. While this limited the value of the data, the problem was further compounded by the variation in the surface properties of each polymorph depending on whether the specimen was a naturally occurring mineral or was made synthetically. Five naturally occurring and 11 synthetically produced titanium dioxide specimens were studied. The physical characterisation of each specimen entailed the determination of the polymorph type(s) by continuous scan x ray diffraction and the size distribution by transmission electron microscopy. The ability of each specimen to lyse erythrocytes was determined and compared with quartz. Only two, both synthetic rutiles, were found to be active. The hydrogen bonding ability of the surfaces of these rutiles were compared with inert rutile and quartz. The binding properties of the active rutile have been found to be consistent with those properties associated with biologically active quartz. The surface properties of rutile are the determinants of its activity. Because natural and synthetic rutiles possess different surface properties, they display different activities.