The possible role of two neuropeptides (substance P and (Met)enkephalin-Arg6-Phe7) in nociception were studied in 14 surgical patients. Lumbar cerebrospinal fluid (CSF) concentrations of the putative excitatory afferent transmitter substance P and the mu and delta receptor agonist (Met)enkephalin-Arg6-Phe7 were measured during general anesthesia for abdominal surgery and during the postoperative period when patient-controlled analgesia (PCA) was used for control of pain. The CSF was sampled through an intrathecal catheter. Seven of the patients were randomly assigned to receive neurolept anesthesia; the rest were given isoflurane anesthesia without narcotics. No statistically significant changes occurred in substance P concentrations in CSF during surgery or postoperative PCA, nor were there significant differences between the two groups. There was, however, a significant correlation between CSF substance P concentrations before the start of PCA and pain assessment on a visual analogue scale. The individual changes in substance P concentrations during PCA was also inversely correlated to the consumption of meperidine. The CSF (Met)enkephalin-Arg6-Phe7 concentrations were below the level of detection in seven of the patients before anesthesia. A large interindividual variability in both substance P and (Met)enkephalin-Arg6-Phe7 concentrations was evident. The absence of major changes in CSF neuropeptide concentrations was unexpected. Apparently inter-individual variations in neuropeptide output are considerable.