Morphine sulfate causes immunomodulatory and immunosuppressive effects in human, In this study, the signaling pathway involved in these morphine effects was studied, Addition of morphine sulfate to human CEMx174 lymphocytic cells resulted in increased ex pression of mitogen-activated protein kinase cascade proteins, Morphine enhanced the cellular levels of ERK1 (44 kDa), ERK2 (42 kDa), a 54-kDa ERK, MEK1 (45 kDa), and MEKK (78 kDa), A time-dependent increase in the activated (Thr and Tyr dually phosphorylated) state of ERK1 and ERK2 was also observed, Naloxone, a morphine antagonist, reversed the observed morphine effects, implicating a mu opioid receptor-mediated process. These findings suggest that mitogen activated protein kinases are important intermediates in signal transduction pathways initiated by morphine receptors in immune cells.