Blood vessels may either constrict or dilate in response to 5-HT, the response being dependent on the species, the vascular bed studied and the condition (healthy or diseased) of the subject studied. Vasoconstriction may be mediated by 5-HT(2A), but, in a variable proportion, also by 5-HT(1B) receptors. The expression and function of 5-HT(1B) receptors is likely to be increased in disease states such as hypertension, cerebrovascular disease and variant angina pectoris. Contractile responses mediated by 5-HT(1B) receptors may be increased in blood vessels with damaged endothelium, but may also be augmented in the presence of low concentrations of other vasoconstrictors such as thromboxane A(2), endothelin-1, prostaglandin F(2alpha), angiotensin II, histamine, noradrenaline, phenylephrine or KCl. Such an augmentation, however, is not a generalized phenomenon, since it does not occur in all vascular beds and is not always induced by all substances mentioned above. Whereas the augmentation seems to depend on increased levels of the second messengers involved, the exact mechanism is not yet completely clear. The augmentation of 5-HT(1B) receptor-mediated contractions may be of relevance in pathophysiological conditions such as variant angina and preeclampsia, where the development of 5-HT(1B) receptors seems to be expedited. Further, augmentation of 5-HT(1B) receptor-mediated contractions may be an important determinant in the case of chest symptoms experienced as a side effect of antimigraine drugs.