Abstract Calcyclin, a cell cycle regulated protein, was recently purified from Ehrlich ascites tumour (EAT) cells and shown to be a calcium binding protein. Here we show that calcyclin monomer and dimer also bind zinc ions. Zinc binding sites seem to be different from calcium binding sites since: preincubation with Ca 2+ lacks effect on the binding of Zn 2+, and Ca 2+ (but not Zn 2+) increases tyrosine fluorescence intensity. Binding of Zn 2+ reduces the extent of the conformational changes induced by Ca 2+, and seems to affect Ca 2+-binding. The data suggest that Ca 2+- and Zn 2+- might trigger the biological activity of calcyclin.