Historically, biomedical research has been conducted almost exclusively with male subjects. A growing number of studies now demonstrate sex differences in analgesia produced both by drugs and by environmental stimuli. This review summarizes the current literature on sex differences in analgesia produced by opioids, cholinergics and other drugs, and by stress, exercise and other environmental manipulations. A brief overview of the physiological mechanisms underlying sex differences in analgesia. is provided, as well as suggestions for future research. It is not yet known whether the development of sex-specific analgesia treatment guidelines is warranted. (C) 2003 Published by Elsevier Science Inc.