We recently observed that prostaglandin E(2) (PGE(2))-mediated suppression of T cell functions could result from an attenuation of p59(fyn) protein tyrosine kinase activity. The present study evaluated the effects of an adenylate cyclase agonist (forskolin) and antagonist (SQ-22536), as well as those of cAMP analogues (dibutyryl cAMP and 8-bromo- cAMP), on T cell p59(fyn) kinase activity. The study allowed us to assess whether PGE(2)-mediated activation of adenylate cyclase by itself or the elevation in intracellular cAMP levels is an integral event in the modulation of anti-CD3-linked p59(fyn) activation in T cells. The experiments were carried out with splenic T cells from male Sprague-Dawley rats. A 30-50% suppression in the autophosphorylation and the kinase activity of p59(fyn) in T cells incubated with PGE(2) or forskolin was observed. Pretreatment of T cells with SQ-22536 prevented significant PGE(2)-mediated inhibition of T cell p59(fyn) kinase activity. In contrast, no change in p59(fyn) autophosphorylation and kinase activity in T cells treated with cAMP analogues was observed. These data suggest that PGE(2)-mediated suppression of p59(fyn) autophosphorylation and kinase activity in T cells is dependent on the activation of adenylate cyclase and independent of the elevation in cAMP levels.