In 30 patients with diagnosed fibromyalgia, the CSF level of immunoreactive substance P (SP) was investigated. Compared to normal values (9.6 +/- 3.2 fmol/ml), all the patients had elevated CSF levels of SP (36.1 +/- 2.7 fmol/ml, range 16.5-79.1 fmol/ml). Anamnestic information from the patients revealed that 53.3% had Raynaud/Raynaud-like phenomenon localized in the fingers, the toes or both. Although SP levels did not differ significantly in patients with or without the Raynaud phenomenon, elevated activity may be present in the peripheral branches of SP neurons which could be responsible for the last (rubor) phase of the triphasic Raynaud's phenomenon. SP levels were significantly higher in patients who were smokers (40.1 +/- 2.7 fmol/ml, range 25.3-64.1 fmol/ml), compared to patients who were non-smokers (29.2 +/- 5.0 fmol/ml, range 16.5-79.1 fmol/ml). We propose elevated CSF levels of SP and the Raynaud phenomenon as characteristic features for fibromyalgia with potential as diagnostic markers of the disease and further that smoking might be an aggravating factor for its pathogenesis or development.