▪ Abstract  Allozyme polymorphisms have been the focus of studies of selection at single enzyme loci, and most involve the enzymes of central metabolism. DNA sequencing of enzyme loci has shown numerous examples of multiple amino acid polymorphisms segregating within electromorphs. The amino acid heterogeneity underlying many allozyme polymorphisms should confound analysis of functional differences and selection. Metabolic control theory proposed that pathways will be insensitive to functional changes in allozymes; however, there is evidence that many polymorphisms modulate fluxes. Studies of model systems have provided detailed evidence for selection acting on enzyme polymorphisms in metabolic genes. There is also evidence that regulatory changes are superimposed on structural changes. Codon bias implies that the functional differences encountered in allozyme studies should be detectable by natural selection; however, amino acid polymorphisms may also represent weakly deleterious mutations. Future studies should connect structural changes with effects on function and stability, and they should emphasize the multilocus nature of responses to selection.