Suboptimal intake of Zn is one of the most common nutritional worldwide problems. Previously, we showed that Zn deficiency produces alterations in lung lipid metabolism in rats. We studied the effect of a Zn-limited (ZL) diet on the expression of the enzymes involved in phosphatidylcholine and cholesterol synthesis. After 2 months of treatment with a ZL diet we found important variations in the lipid content of Wistar male rats: triacylglycerol (TG) decreased 60% (P<0.001) while esterified cholesterol (EC), free cholesterol and phospholipids (PL) increased 66%, 24 % and 25% respectively. We also observed a decrease of 40 % in the amount of (3)H incorporated into TG and an increase of 47% and 28% in the (3)H incorporated to PL and EC respectively. Fatty acid synthase and glucose-6-phosphate dehydrogenase activity was increased (P<0.01 and P<0.05 respectively). Glycerol-3-phosphate acyltransferase, lipoprotein lipase, diacyl glycerol acyl transferase and 3-hydroxy-3-methylglutaryl CoA reductase expression decreased (P<0.01 in all cases), while acetyl CoA carboxylase and cholinephosphate cytidylyltransferase increased (P<0.01 and P<0.005 respectively). These results suggest that ZL alters the expression of enzymes involved in phosphatidylcholine and cholesterol synthesis, which could lead to increased PL and cholesterol and decreased TG. This study suggests that major changes in the lipid composition of lung are induced by a ZL condition. Therefore, Zn deficiency must be taken into account in order to design therapies and public health interventions, such as Zn supplementation for high-risk subjects or certain diseases, such as asthma.