A number of studies have found positive associations between allozyme heterozygosity and fitness surrogates (e.g., body size and growth rate) for marine molluscs. We investigated whether similar relationships exist for freshwater populations of the zebra mussel, Dreissena polymorpha. Only one significant correlation between multi-locus heterozygosity and shell length was observed for a total of 22 D. polymorpha populations surveyed from midwestern U.S.A. lakes and streams, and the result was not significant on a table-wide basis. Meta-analysis revealed a significant common correlation coefficient (effect magnitude) between multi-locus heterozygosity and shell length across all 22 sites (rc = 0.052, P = 0.019, 1557 df). However, the variance in shell length explained by multi-locus heterozygosity was small (rc2 = 0.0027), implying a weak causal relationship if any. Also, we saw no relationship between heterozygosity and growth rate in a one-year field enclosure experiment. A significant heterozygosity-shell length correlation previously reported for a zebra mussel population at Put-in-Bay, Lake Erie, Ohio, may have been the product of unique population dynamics, rather than natural selection. Similar demographic considerations may contribute to inconsistencies in heterozygosity-fitness correlations seen for other molluscs.