The effects of elevated glucose and eicosapentaenoic acid (EPA, C20:5 omega 3) on myo-inositol uptake in human skin fibroblasts (HSF) were evaluated. Myo-inositol incorporation into HSF was dependent on an active transport system via Na(+)-K+ ATPase activity based on the results with Na+ deprivation and ouabain (5 mM). Although glucose (27.5, 55 mM) inhibited 2-[3H] myo-inositol uptake, the addition of EPA (3 x 10(-4) M) prevented glucose-mediated inhibition. Since EPA decreased glucose-mediated inhibition of myo-inositol uptake, this agent might ameliorate some of the devastating functions associated with diabetes.