Previous work in this laboratory has shown that adrenal medullary transplants into the spinal cord subarachnoid space can reduce pain sensitivity. This analgesia most likely results from the release of neuroactive substances, particularly catecholamines and opioid peptides, from the transplanted cells into the CSF of the spinal cord, since it can be attenuated or blocked by alpha-adrenergic or opiate antagonists. The purpose of the present study was to more directly measure the release of catecholamines from adrenal medullary transplants in the spinal cord CSF using a spinal superfusion technique. CSF samples from rats with 6-month-old transplants were assayed for catecholamines using HPLC with electro-chemical detection. Results indicated that norepinephrine levels were increased threefold, and epinephrine levels nearly 100-fold, in animals with adrenal medullary transplants compared with control transplanted animals. There was no apparent increase in dopamine levels. Furthermore, the increased levels of total catecholamines were correlated with decreased pain sensitivity. Results of this study indicate that adrenal medullary transplants can survive for long periods in the rat spinal CSF and continue to release high levels of catecholamines. Together, the release of catecholamines and opioid peptides from adrenal medullary transplants may provide the ideal combination for the reduction of pain.