Substantially less genetic variation has been recognized in studies of the proteins of nucleated cells by the technique of two-dimensional polyacrylamide gel electrophoresis than has been encountered in studies of serum transport proteins and erythrocyte enzymes with one-dimensional electrophoresis. Technical factors appear to account for only part of the difference. The two remaining (nonexclusive) explanations are more stringent biological selection against variants of these proteins or lower mutation rates at the loci encoding the proteins visualized with two-dimensional electrophoresis. While the former possibility cannot be rigorously excluded, the evidence suggests the latter hypothesis merits serious consideration. Some consequences of this latter suggestion for genetic monitoring and the interpretation of molecular evolution are mentioned.