The intake of mono- and polyunsaturated fatty acids has been associated with a minor risk of cardiovascular diseases including hypertension. Changes in levels of fatty acids may also modify the cell activity and may be related with alterations in different regulatory processes. Aminopeptidases are zinc-metalloenzymes which metabolise circulating peptide hormones in several tissues. Glutamyl-aminopeptidase (GluAP) and to a lesser extent, aspartyl-aminopeptidase (AspAP), are related with angiotensin metabolism in the renin-angiotensin system. The present work was designed to study the effect of a range of concentrations (1-100 microM) of oleic and linoleic acids and cholesterol present in the culture medium on the activity of GluAP and AspAP in the culture of rat cerebral cortical astrocytes taken from 21-day-old fetuses. The results showed that oleic acid inhibits, while linoleic acid stimulates the activity of AspAP. Both fatty acids inhibit the activity of GluAP. Cholesterol stimulates the activity of both enzymes. On the basis of these results, a functional link may exit between the effects of fatty acids on hypertension and the modulation of aminopeptidase activity by these compounds in rat astrocytes, as an example of target cell type in the central nervous system.