Intraplatelet and plasma serotonin (5-HT) levels were measured in 39 patients with systemic lupus erythematosus (SLE) and in 15 healthy subjects. Urinary 5-HT concentrations were also measured in 32 patients with SLE and 14 healthy subjects. A significantly lower intraplatelet 5-HT level was observed in SLE patients, especially in the active phase with hypocomplementemia (CH50 less than 30 U/ml), 0.17 +/- 0.09 pmol/10(5) platelets, than that in normal controls, 0.36 +/- 0.14 pmol/10(5) platelets (p less than 0.01). Active SLE showed a significantly higher urinary 5-HT concentration, 0.37 +/- 0.15 nmol/ml/mg Cr, than normal controls, 0.21 +/- 0.08 nmol/ml/mg Cr (p less than 0.01). Serial measurements of intraplatelet and urinary 5-HT levels in five patients with SLE revealed a significant correlation between clinical activity and intraplatelet and urinary 5-HT levels. Exogenous 5-HT uptake by platelets in vitro is not altered in patients with SLE. The mechanism of decrease of intraplatelet 5-HT and increase of urinary 5-HT in SLE may be explained by the continuous activation of the blood coagulation within the vessel.