['Opioids and anticancer compounds such as etoposide (ETP) are substrates of P-glycoprotein (P-gp), an ATP-dependent efflux pump. Chemotherapy compounds may impact on the analgesic effect of opioids such as morphine when the two drugs are co-administered. In this study, we used a mouse model to determine if there is a pharmacological interaction between ETP and morphine, focusing on the involvement of intestinal P-gp.', 'P-gp drug efflux activity was measured by an in-situ closed loop method with Rhodamine 123, a P-gp substrate. The analgesic effect of morphine was determined by the tail-flick test. Intestinal P-gp expression levels were determined by Western blot.', 'ETP and morphine significantly decreased the intestinal Rhodamine 123 efflux activity of P-gp. Oral morphine analgesia was significantly enhanced when co-administered with ETP. However, repeated pretreatment (7 days) with oral ETP significantly decreased the oral morphine-induced analgesia, in a cyclosporine A (a P-gp inhibitor) reversible manner. Furthermore, repeated ETP significantly up-regulated intestinal P-gp expression.'] Does etoposide modulate the effects of oral morphine analgesia by targeting the intestinal P-glycoprotein?