We performed experiments in human cerebral arteries to determine the source of activator calcium during contractions induced by 5-hydroxytryptamine. Rings of human basilar artery obtained at autopsy were mounted for isometric tension recording in organ baths filled with a physiological salt solution. Contractile responses to 5-hydroxytryptamine were virtually abolished in Ca++-free solution, and inhibited significantly by nimodipine. In both cases, the depression of the response to 5-hydroxytryptamine was comparable to that seen when KCl was used to contract the vessels. These experiments demonstrate that 5-hydroxytryptamine mediates contraction of the smooth muscle in human basilar artery by increasing membrane permeability to extracellular calcium.