Anaesthetists, using basic scientific concepts of peripheral opioid activity, try to improve regional anaesthesia and postoperative analgesia by injecting opioids, with or without local anaesthetic, close to nerve trunks or nerve endings. To test the evidence that peripherally applied opioids (all except intra-articular) have an analgesic effect outside the knee joint. Systematic search for published reports of randomised controlled trials in the period 1966–1996 (MEDLINE, EMBASE, Oxford Data Base, reference lists) which compared efficacy of peripheral opioids with placebo, local anaesthetic, or systemic opioids in acute pain. Reports of pethidine or intra-articular opioids were not included. Data on intraoperative efficacy (onset, quality, duration of sensory block), and postoperative efficacy (pain intensity, analgesic consumption) were extracted. Statistical significance as indicated in the original reports and clinical relevance of differences between opioids and controls were taken into account to estimate qualitatively overall efficacy. Twenty-six trials with data from 952 patients were analysed. Opioids used were morphine (16 trials), fentanyl (8), alfentanil (1), buprenorphine (1), and butorphanol (1). Of four experimental pain trials, two reported a statistically significant difference in favour of the opioid. In 22 clinical trials efficacy of opioid injections into the brachial plexus (10), Bier's block (4), perineural (3), or other sites (5) was tested. Five of 10 clinical trials measuring intraoperative efficacy reported statistically significant efficacy with opioids compared with control; none of them were judged to be clinically relevant. Five of 17 clinical trials measuring postoperative efficacy reported a significant difference in favour of the opioid; none was judged to be clinical relevant. Trials of lower quality were more likely to report increased efficacy with opioids. Adverse events related to the route of administration were not reported. These trials provide no evidence for a clinically relevant peripheral analgesic efficacy of opioids in acute pain.