The present results demonstrate an antagonistic effect of DNS-RFa on morphine-induced analgesia in rats. This confirms previous evidence presented by others on the effects of FMRFa-related peptides when applied centrally. Unlike these peptides, however, it is shown here that DNS-RFa is effective upon peripheral injection. The effects of DNS-RFa on morphine-induced analgesia were dose-dependent (ED50=0.5 mg/kg). DNS-RFa alone (5 mg/kg) did not affect the control level of nociception. Peripheral injection of FMRFa (5 mg/kg) did not affect morphine-induced analgesia. DNS-RFa defines the minimal configuration to activate neuronal FMRFa receptors in the pond snail (4). The present report suggests also that in vertebrates the Arg-Phe-NH2 sequence is essential and that DNS-RFa readily penetrates the blood-brain barrier. © 1989.