Freshwater mussel assemblages in the Flint River Basin (FRB) of southwestern Georgia are among the most diverse in the southeastern Coastal Plain of North America. Historically, 29 species, including 7 endemics, occurred in the FRB. A drought during the summer of 2000 caused record low flows and many perennial streams dried or became intermittent. Predrought surveys conducted in 1999 allowed an assessment of the impact of the drought on mussel assemblages. During 2001, 21 stream reaches that had abundant or diverse mussel assemblages in 1999 were resurveyed. Study sites were classified as flowing or non-flowing during the drought based on data from stream gauging stations or visual observation of study reaches. Mussels were classified by conservation status, either stable, special concern, or federally endangered. Greater than 90% of the mussels observed in the lower FRB were species with stable conservation status. Special-concern species represented 5 to 6% and endangered species represented 1% of mussel abundance. Sites that ceased flowing during the drought had significant declines in the abundance of stable species and in taxa richness. Endangered species also showed evidence of a decline in non-flowing sites. Sites that maintained flow had increases in stable species and no change in special concern, endangered species, or species richness through the drought. Sites that showed declines in mussel abundance had a significantly lower frequency of wood debris than other sites. Field observations suggested that shallow depressions beneath wood debris may act as refuges for freshwater mussels during stream drying. Greatest declines in mussel abundance usually occurred in the mid-reaches of the major tributaries of the lower Flint River. These reaches depend on the Upper Floridan aquifer, which is heavily used for irrigation, to maintain base flows. Declines in mussel populations appear to be associated with unusual climatic conditions and increasing demand on the area streams and the regional aquifer system for irrigation water supply.