Enhanced-fluidity liquids (EFL), also called gas-expanded liquids (GXL), are solvent mixtures containing high proportions of a liquefied gas. These liquid mixtures have mass transport properties (rates of diffusion and viscosity) that are intermediate between those of liquids and supercritical fluids. Significant increases in the rate of diffusion cause corresponding improvements in the chromatographic efficiency. Another strong attribute of EFLs is that while the mass transport properties are improved by adding large proportions of liquefied gases, the solvent strength of the liquid is maintained to a value close to that of the original mixtures. In the past, we have shown that by using EFLC, the speed of the separation and the efficiency improve for mixtures of moderately polar analytes. We are currently moving this technology toward applications that include highly polar mixtures, such as those in biological systems. For example, nucleotide and nucleoside separations without gradient elution methods are now viable.