The vasoactive agent 5-hydroxytryptamine (5-HT) has been implicated in human heart valve disease, which may be due to possible trophic effects on valve interstitial cells (IC). In the present study, the responses of cultured human heart valve IC to 5-HT and angiotensin II (Ang II) were monitored in terms of intracellular calcium concentration , mitogenesis and collagen synthesis. Both 5-HT and Ang II triggered sharp increases in calcium concentration in human valve IC. In addition 5-HT, but not Ang II, was weakly mitogenic towards quiescent IC. Furthermore, valve IC responded positively to both 5-HT and Ang II with increases in collagen synthesis. We conclude that 5-HT and Ang II promote the prolonged processes of growth and collagen synthesis in cultured human valve IC. This indicates that these agents may play a role in the development of heart valve disease.