The contribution of intra- and extracellular Ca++ during KCl- and 5-hydroxytryptamine-induced contractions was investigated in human isolated umbilical arteries obtained from cords of normal full-term deliveries. In normal solution, nifedipine caused dose-dependent relaxations of the arteries contracted by high K+ (80 mM) and 5-hydroxytryptamine. The IC50 value of nifedipine on KCl-induced contractions was about 9 times lower than that on 5-hydroxytryptamine-induced contractions. In Ca(++)-free medium, KCl failed to induce contractions of the artery. However, 5-hydroxytryptamine caused contractions amounting to 52% of the maximum response obtained by re-addition of Ca++, and this response was abolished by 10(-6) M of nifedipine. In the presence of either KCl or 5-hydroxytryptamine, subsequent addition of Ca++ caused reproducible contractions which were also inhibited by nifedipine. These results indicate that the KCl-induced contraction of human isolated umbilical artery is mainly dependent on extracellular Ca++, whereas that induced by 5-hydroxytryptamine involves both intra- and extracellular Ca++. It is also suggested that nifedipine does not only inhibit the influx of extracellular Ca++ during the contraction by 5-hydroxytryptamine but that it may also have intracellular effects.