While studying the enzymatic processing of arachidonic acid (AA) to eicosanoids in homogenates of hippocampal astrocytes, we observed that all the HPLC peaks corresponding to AA metabolites displayed significantly different levels depending on the presence or not of free Ca2+ in the incubation medium. A specific pattern was noticed, i.e. lipoxygenase (LOX) derivatives, in particular 12-hydroxyeicosatetraenoic acid (12-HETE), showed higher levels in medium containing 1 mM Ca2+, while cycloxygenase (COX) products including prostaglandins (PG) F2 alpha, E2 and D2 and 12-hydroxyhepatadecatrienoic acid (12-HHT), were higher in Ca(2+)-free medium. COX metabolism exceeded LOX metabolism by threefold in Ca(2+)-free medium, while it was only 60% of it in 1 mM Ca2+. The total amount of AA processed under the two conditions was identical. These data suggest that free [Ca2+] influences the pattern of AA metabolites formed in hippocampal astrocytes, with possible important implications in view of the distinct roles played by COX and LOX eicosanoids in synaptic transmission and neurotoxicity in this area.