The specificity of an enzyme obeying the Michaelis-Menten equation is normally measured by comparing the k(cat)/K-m for different substrates, but this is inappropriate for enzymes with a Hill coefficient h different from 1. The obvious alternative of generalizing K-m in the expression as K-0.5, the substrate concentration for half-saturation, is better, but it is not entirely satisfactory either, and here we show that k(cat)/K-0.5(h) gives satisfactory results for analyzing the kinetic behavior of metabolic pathways. The importance of using k(cat)/K-0.5(h) increases with the value of h, but even when h is small, it makes an appreciable difference, as illustrated for the mammalian hexokinases. Reinterpretation of data for the specificity of these enzymes in terms of the proposed definition indicates that hexokinase D, often believed highly specific for glucose, and accordingly called "glucolcinase", actually has the lowest preference for glucose over fructose of the four isoenzymes found in mammals.