Opiate addiction has been reported to contribute to the progression of renal injury. In addition, opiate addiction is a major risk factor for the development of HIVAN. In the present study, we evaluated the effects of morphine, an active metabolite of heroin, on glomerular epithelial cell (GEC) growth and the involved molecular mechanism. Morphine at lower concentrations promoted GEC proliferation; however, at higher concentrations morphine triggered apoptosis. Anti-oxidants inhibited both morphine-induced proliferation as well as apoptosis. Similarly, free radical scavengers prevented morphine-induced GEC proliferation and apoptosis. Since both proliferative and proapoptotic effects of morphine were inhibited by free radical scavengers as well as antioxidants it appears that these effects of morphine are mediated through oxidative stress. Hemin, an inducer of heme oxygenase (HO)-activity, inhibited GEC proliferation and promoted GEC apoptosis both under basal and morphine stimulated states. On the other hand, zinc protoporphyrin (Zn-P), an inhibitor of HO activity, promoted GEC proliferation and inhibited GEC apoptosis under basal as well as morphine stimulated states. These findings suggest that HO-activity has a direct relationship with GEC apoptosis and an inverse relationship with GEC proliferation. Morphine, de novo, had bimodal effects on HO activity-lower concentrations increased and higher concentrations decreased HO activity. It appears that HO activity may be modifying morphine-induced GEC growth.