Abstract;The white spot syndrome virus (WSSV) is the causative agent of a severe disease in cultivated shrimp. The virus causes high mortality and leads to heavy stress on shrimps. In response to a variety of stresses, living organisms express particular sets of genes such as HSPs. In this study, a HSP21 gene, categorized into the small heat shock protein (smHSP) family, of shrimp Penaeus monodon was identified by annotating the EST databases established from WSSV-infected and WSSV-uninfected shrimp. The shrimp HSP21 gene was 555 bp in length. The thermal aggregation assay showed that the HSP21 had chaperone activity. The result of real-time PCR indicated that HSP21 was constitutive and inducible and was highly expressed in almost all organs such as the epithelium, gill, stomach, midgut, lymphoid organ, hepatopancreas, nervous tissue and heart, but less expressed in haemolymph. However, HSP21 gene showed down-regulation after WSSV infection. It suggests that gene regulation of HSP21 was seriously affected by WSSV.