L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxy-tryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator for pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) higher than that after L-5HTP alone. Neither subjective pain threshold and tolerance nor RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception.