In this study, we have compared the time-course effects of lipopolysaccharide (LPS) and interleukin-1beta on prostaglandin (PG) production by primary cultures of rat astrocytes. At variance with interleukin-1beta, LPS produced significant increases in PGE2 release after only 1 h of incubation, an effect unlikely to depend on new protein synthesis; the involvement of constitutive cyclooxygenase (COX-1) was therefore investigated. Experiments with acetylsalicylic acid showed that 80% of PGE2 production after 1 h of treatment with LPS is accounted for by COX-1; this figure decreases to about 30% after a 24-h treatment. The increase in PGE2 production occurring after a 24-h challenge with the endotoxin seems to involve the activation of phospholipase A2. In fact, LPS-stimulated PGE2 release was significantly reduced by a peptide from the primary sequence of lipocortin-1, peptide Ac2-26, which was previously shown to inhibit phospholipase A2 in several in vitro models.