The inhibition of human lens aldose reductase by flavonoids has been studied. Quercetin, the major pentahydroxyflavone, was observed to inhibit human lens aldose reductase by 50% at a concentration of 5 X 10(-6) M. The inhibitory activity of its 3-O-glucoside was similar to that of the parent aglycon. Glycosidation with L-sugar (quercitrin and guaijaverin), however, improved the inhibitory activity (the IC50 values being 1 X 10(-6) M and 2.5 X 10(-6) M respectively). The improvement in inhibitory activity with glycosidation with L-sugar was also apparent from the high inhibitory activity of myricitrin as compared to myricetin, although the improvement in this case of hexahydroxy flavone glycosidation was significantly less than in the case of penthahydroxy flavone glycosidation. The structure-activity relationship observed for human lens enzyme was similar to that reported previously for rat lens enzyme. Inhibitory activity on the whole however, was lower with human lens enzyme. Some known inhibitors of cyclo-oxygenase such as indomethacin, aspirin and sulindac also inhibited human lens aldose reductase. Thus, an inhibitor of one of the enzymes may actually inhibit both and, when administered, may exert mixed physiological effects.