The short-term tissue responses to two potential root-end filling materials, a light-cured glass ionomer cement (Vitrebond) and a reinforced zinc oxide–eugenol cement (Kalzinol), were compared with that to amalgam using a previously devised experimental model. In 24 premolar teeth of beagle dogs (47 roots), a collection of endodontic pathogenic bacteria was first inoculated into the root canals to induce periradicular lesions. On each root, an apiccctomy was performed and root-end cavities prepared to receive fillings of each material. The teeth and surrounding jaw were removed after 2 weeks (23 roots) and 1 week (24 roots); they were then prepared for histological examination. The tissue response to amalgam fillings after 2 weeks and 1 week was marked by moderate or severe inflammation on all roots, and extended to 0.5 mm or >0.5 mm in 15 out of 16 roots. In contrast, after 2 weeks, the majority of roots filled with Kalzinol showed little or moderate inflammation, while the tissue response to Vitrebond was the best of the three materials, and was also the least extensive. After 1 week, the overall best tissue response was with Vitrebond, followed by Kalzinol. The differences between materials for both time periods with either none or few inflammatory cells when compared with that with either moderate or severe inflammation were not statistically significant (P<0.02). However, the differences between materials for both time periods with no inflammation or inflammation extending <0.2 mm when compared with that with inflammation extending >0.2 mm (0.5 mm or >0.5 mm) were statistically significant (P<0.01). Apart from amalgam, in which healing was marked by the persistence of a localized focus of inflammation adjacent to the root-end filling, even though there were intersamlpe variations, there was little overall difference in the temporal and qualitative healing response to Vitrebond and Kalzinol. Both Vitrebond and Kalzinol have potential as root-end filling materials, as the tissue response was considerably more favourable than that to amalgam even in the short-term.