The pathophysiologic effects of infusing unstable lipid emulsions are unclear, but these were shown to cause reticuloendothelial system (RES) dysfunction in animals and humans. We investigated the effects of unstable lipid emulsions in RES organs defined by two levels of the percent fat >5 microm (percentage of fat, PFAT>5 microm) in a guinea pig model. Two identical injectable lipid emulsions with differing (stable versus unstable) PFAT >5 microm levels, were infused for over 24h into two groups of animals (n=5/group). The PFAT>5 microm concentration was measured before and at the end of the infusion to ascertain the dose range of enlarged fat globules in each group. Animals were euthanized and specimens from the upper, middle and lower lung, and a single liver sample were examined histologically and for micromolar concentrations of malondialdehyde (MDA) per gram (micromol(-1)g) of wet tissue. The PFAT>5 microm concentrations pre-infusion were 0.004+/-0.001 and 2.418+/-0.273 for the stable and unstable injectable lipid emulsions respectively. At 24 h, the PFAT>5 microm level increased in both the groups (stable: 0.161+/-0.008; unstable: 7.861+/-0.291). MDA concentrations were significantly higher in the lungs of animals receiving the unstable (47.2+/-26.2 micromol(-1)g) versus stable (32.4+/-11.2 micromol(-1)g) injectable lipid emulsions (P=0.033), but was not different for the liver specimens (stable: 16.9+/-7.6 micromol(-1)g versus unstable: 17.7+/-2.2 micromol(-1)g, P=0.944). These preliminary data suggest that infusion of unstable injectable lipid emulsions has pathological consequences showing greater evidence of oxidative stress in the lungs.