Peripheral blood concentrations of the proinflammatory peptide substance P (SP) have been shown to increase in response to psychological anxiety in human subjects. In this study, we examined changes in SP levels in peripheral blood in response to the anxiety of a diagnostic medical procedure. The levels of SP were found to be higher in subjects with high initial anxiety as compared to subjects with low initial anxiety as measured on the Multiple Affect Adjective Checklist. Changes in the percentages of CD-8-expressing T lymphocytes were found to correlate with alterations in measures of anxiety as well as SP. These changes persisted for 3 days following the diagnostic procedure. The results of the study seem to indicate that SP may serve as a mediator in stress-induced immune reactions.