Allozyme data and DNA strand break frequencies were compared among populations of Pleurocera canaliculatum from five sites with varying mercury contamination on the North Fork Holston River (NFHR) in southwestern Virginia, USA. Allozyme genotype frequencies for four loci were significantly different between populations from the three most highly contaminated sites and those from two lesser contaminated sites. In addition, heterozygosity at three of these loci was significantly lower in the populations from the most highly contaminated sites. The DNA strand break frequency was significantly correlated to whole-body total mercury concentration in snails from three sites. These data add to the evidence supporting the use of DNA strand breakage as an indicator of chemical contamination and the use of allozyme analysis as a marker of contamination and possible selection for pollution resistance. However, the relationship between contaminant-induced changes in the genetic variation of enzymes of central metabolism and the functionalities upon which selection for resistance may act remain unclear, and mechanisms other than selection for resistance must be considered. Use of enzymes from other biochemical pathways may be appropriate for other species or for those under other chemical pollution pressures.