Objectives: To investigate the role of serotonergic pathways as a potential factor modulating pain in general and nonarticular tenderness in particular. Methods: Twenty healthy volunteers were given metergoline [a nonspecific serotonin blocker] once and placebo once, in a double blind, placebo-controlled, randomized crossover design. The administrations were separated by at least one week. In each session a count of 18 tender points was conducted by thumb palpation just before and 90 minutes after capsule ingestion. Tenderness of nine of the tender points as well as four control points was further assessed with a Chatillon dolorimeter. Results: There was no significant difference in the point count or in tenderness in the presence or absence of serotonin blockade. Conclusions: Serotonin blockade in healthy individuals has no effect on the point count or on tender point sensitivity. This suggests that involvement of serotonergic pathways does not contribute to pain syndromes associated with nonarticular tenderness, or, alternatively, that studies of nonarticular tenderness in healthy volunteers are not relevant to the same phenomenon in clinical syndromes.