Many studies have focused on the relationships between distinct enzymatic sources of oxidative mediators. Recently, we have shown that cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (NOS-2) isoforms are up-regulated and account for oxidative damage in brain after stress. To assess the time course of these events, we have used adult male Wistar rats, some of which were immobilized for 6 h. Whereas pretreatment with the specific COX-2 inhibitor NS-398 (5 mg/kg i.p.) decreased Ca2+-independent NOS activity after 6 h of stress, pretreatment with the specific NOS-2 inhibitor 1400 W (4 mg/kg i.p.) did not decrease prostaglandin E2 (PGE2) accumulation induced by stress after 6 h. The observed effects of NS-398 and 1400 W were independent of the general response to stress – neither drug modified stress-induced corticosterone response – which might indicate a possible adaptive role for COX-2 and NOS-2 pathways in this situation. These findings are discussed as possible therapeutic targets in the context of neuropsychiatric disorders related to stress.