An atomic force microscopy (AFM)-based nanoindenter was used to evaluate the mechanical properties of skeletal bones in wild-type and gene-mutated zebrafish (Danio rerio), stopsel(dt128d). Both skeletons were isolated from adult zebrafish and tested under a load of 5 mN. It was found that stp/stp bone has a similar nanohardness but significantly greater elastic modulus compared with that of wild-type bone. The residual indenter impressions using AFM and the fracture surfaces of both bones using scanning electron microscopy were examined and showed that the bone of zebrafish becomes more brittle after the stp mutation. This first observation of the alteration of bone mechanical behavior by gene mutation in zebrafish system is of scientific and clinical relevance to many areas of study, such as bone fracture and fragility mechanisms in human heritable disorders and bone-materials fabrication via gene engineering. (Bone 30: 541-546; 2002) (C) 2002 by Elsevier Science Inc. All rights reserved.