Objective: The choice of analgesia in the management of post-thoracotomy pain remains controversial. Although several alternative forces of post-thoracotomy analgesia exist, all have their disadvantages. Cryoanalgesia, localized freezing of intercostal nerves, has been reported to have variable effectiveness and an incidence of Ion-term cutaneous sensory changes. We carried out an animal study to assess the reversibility of histological changes induced by cryoanalgesia and a prospective randomized trial to compare the effectiveness of cryoanalgesia with conventional analgesia (parenteral opiates). Methods: In six anaesthetized dogs, intercostal nerves were exposed to a varying duration of cryo-application (30, 60, 90 and 120 s). The nerves were biopsied and examined histologically at regular intervals over the following 6 months. In the clinical study, 200 consecutive patients undergoing thoracotomy were randomized to cryoanalgesia and conventional (parenteral opiates) analgesia groups. Postoperative pain scores, respiratory function tests and use of opiate analgesia were measured for the two groups. Results: Following application of the cryoprobe, degeneration and fragmentation of the axons was evident with associated inflammatory changes. As the endoneurium remained intact, axonal regeneration took place after the resolution of axonal swelling. Over the course of weeks,, recovery of the intercostal nerve occurred and was complete after I month for the 30 and 60 s groups. For nerves exposed to longer durations of cryoanalgesia, the time taken for complete recovery was proportionally increased. Clinically, there was a statistically significant (P<0.05) improvement in postoperative pain scores and use of opiate analgesia and an improvement (P>0.05) in respiratory function tests for patients in the cryoanalgesia group. The previously suggested cutaneous sensory changes resolved,within 6 months with complete restoration of function. Conclusions: We suggest that cryoanalgesia be considered as a simple, inexpensive, long-term form of post-thoracotomy pain relief, which does not cause any long-term histological damage to intercostal nerves. (C) 2001 Elsevier Science B.V. All rights reserved.