Only β-NGF, the subunit of the 7S NGF complex, exhibits NGF activity, but the function ofthe zinc ion in native β-NGF has received little attention. Flameless atomic absorption spectroscopy (FAAS)measurements reveal that native β-NGF contains Zn(II) with a Zn(II)/β-NGF stoichiometry of 1:14.6.The presence of Zn(II) in the native molecule results in significant changes of the secondary structure andlocal tertiary structure around Trp(s) with respect to those of apo β-NGF, as suggested by spectra offluorescence and circular dichrosim. Stopped-flow studies show that there are at least two steps during theinteraction of Zn(I1) with the apo form. In comparison with its apo form, the native β-NGF shows a higherability to trigger the proliferation of TF 1 cells and mediate the survival of PC 12. Thus it is most likely that thestructural changes caused by the presence of Zn(II) directly lead to the increase in the biological activity ofβ-NGF. All results indicate that Zn(II) in native β-NGF plays an important role in the structure and thebiological activity of the protein.