Both warm water tail-withdrawal and respiratory assays have been used to characterize the behavioral effects of various opioid compounds in monkeys. In particular, both assays serve as valid in vivo endpoints for studying the efficacy and selectivity of opioid agonists and the characteristics of opioid antagonists. We have further established an experimental model of inflammatory pain as well as intrathecal and intracisternal injection techniques in monkeys. The proposed research will provide a valuable opportunity to enhance the pharmacological study of pain and opioids in non-human primates. Although there are many interesting findings from rodent studies, it is not clear to what extent they can be replicated and applied to primate species. It is important to conduct monkey studies for characterizing novel, experimental compounds, which have been proposed as better analgesics with less side effects in rodents. This series of proposed studies has several aims including studying different aspects of nociceptive mechanisms, evaluating distinct or newly developed opioid agonists and antagonists, and evaluating the roles of other receptor populations in nociceptive transmission. These studies will also clarify the site(s) of action of novel analgesics, comparing the antinociceptive efficacy of exogenous and endogenous opioid ligands; they will study the non-opioid influence of certain important pain-related substances (e.g. serotonin) for their influence on opioid actions in primates. They will provide a better understanding of opioid pharmacology in general and make a substantial contribution to pain research in primates.