The conformational changes of carboxymethyl dextran (CMD) substrates induced by variations in pH and ionic strength were studied using surface plasmon field-enhanced fluorescence spectroscopy (SPFS). A typical response was an increase in swelling upon increasing the pH and decreasing the ionic strength. Furthermore, the effects of the surface charge and cross-link density of the CMD on the degree of stimulus responses were investigated. The swelling/ collapse ratio decreased with decreasing carboxyl group surface concentration and increasing cross-link density.