To determine the role of amelogenin in the mineralization of dental enamel, the effects of the recombinant mouse amelogenin rM179 on in vitro hydroxyapatite formation have been studied. In a steady-state agarose gel assay for hydroxyapatite nucleation, rM179 lacked significant activity at concentrations up to 300 microgram/ml. In an autotitration assay for inhibition of de novo hydroxyapatite formation, rM179 had no significant activity at concentrations up to 30 microgram/ml. Using selected-area dark-field electron microscopy, it was shown that rM179, at concentrations up to 30 microgram/ml, did not significantly affect the length of hydroxyapatite crystals formed in steady-state agarose gels. These findings suggest that amelogenins do not possess the specific crystal-modulating properties characteristic of certain acidic mineralized tissue proteins proteins.