Ligation of macrophage alpha(2)-macroglobulin signalling receptors (alpha(2)MSR) with activated alpha(2)-macroglobulin (alpha(2)M*) increases intracellular Ca(2+), and cytosolic phospholipase A(2) (cPLA(2)) and phospholipase D activities. In view of the relationship between cellular Ca(2+) and mitogenesis, we examined the effect of the product of cPLA(2) activity, arachidonic acid (AA), on nuclear Ca(2+) levels in macrophages stimulated with alpha(2)M*, platelet derived growth factor, and bradykinin. AA addition increased Ca(2+) levels in Fura-2/AM loaded nuclei from both buffer-treated and agonist-stimulated cells, but the increase in stimulated macrophages was 2-4-fold higher. Preincubation of Fura-2/AM loaded nuclei with EGTA or BAPTA/AM abolished AA-induced increase in nuclear Ca(2+) levels. Preincubation of nuclei with indomethacin did not affect AA-induced increase in nuclear Ca(2+) in agonist-stimulated nuclei. It is concluded that in macrophages stimulated with various agonists, AA, derived from cPLA(2)-dependent hydrolysis of phospholipids, plays a significant role in regulating nuclear Ca(2+) levels and thus nuclear functions.