The effect of dietary omega-3 polyunsaturated fatty acids on the lipid composition and fluidity of erythrocyte membranes, and on in vivo insulin sensitivity was studied in 6 non-insulin-dependent diabetic (NIDD) patients. An 8 weeks daily supplementation of 3 g of the omega 3 fatty acids eicosapentaenoic and docosahexaenoic acid resulted in an increase of the membrane phospholipid unsaturation and the sphingomyelin content. Erythrocyte membrane fluidity, measured with electron spin resonance of intact erythrocytes and with fluorescence polarization of erythrocyte ghosts, did not change. The in vivo insulin stimulated glucose uptake was estimated by determining the metabolic clearance rate (MCR) of glucose in the steady state of a simultaneous infusion during 150 min of glucose (33 mumol/kg/min) and insulin (50 mU/kg/hr). The MCR of glucose increased in all patients; from 3.93 +/- 0.55 - 4.69 +/- 0.74 ml/kg/min (mean +/- SEM, p less than 0.05). Plasma triglyceride concentrations fell from 1.9 +/- 0.3 - 1.2 +/- 0.2 mmol/l (mean +/- SEM, p less than 0.05). We conclude that in NIDDs dietary supplementation of omega 3 fatty acids improves in vivo insulin sensitivity and lowers plasma triglyceride levels, while erythrocyte membrane fluidity remains unaltered.