The aim of the present study was to evaluate histologically in humans the healing of advanced intrabony defects following treatment with enamel matrix proteins (EMD) or guided tissue regeneration (GTR). Fourteen patients, each of them displaying 1 advanced intrabony defect around teeth scheduled for extraction were included in the study. The defects were treated randomly either with an enamel matrix protein derivative (Emdogain, BIORA AB, Malmö, Sweden) or with a bioabsorbable membrane (Resolut, Regenerative Material, W.L. Gore & Assoc., Flagstaff, Arizona, USA). At baseline the mean probing pocket depth (PPD) in the EMD group was 11.3 +/- 1.8 mm and the mean clinical attachment level (CAL) 12.1 +/- 2.0 mm, whereas in the GTR group the mean PPD was 11.4 +/- 2.2 mm and the mean CAL 13.3 +/- 2.3 mm. Healing was uneventful in all cases. Neither allergic reactions against EMD or the bioabsorbable membrane, nor suppuration or abscesses were observed. The clinical results revealed at 6 months in the EMD group a mean PPD of 5.6 +/- 1.3 mm and a mean CAL of 9.1 +/- 1.5 mm. In the GTR group the mean PPD was 5.6 +/- 1.3 mm and the mean CAL 10.1 +/- 1.5 mm. The histological analysis showed in the EMD group a mean 2.6 +/- 1.0 mm of new attachment (i.e. new cementum with inserting collagen fibers) and a mean 0.9 +/- 1.0 mm of new bone. In this group, the formation of new attachment was not always followed by bone regeneration. In the GTR group, the mean new attachment was 2.4 +/- 1.0 mm and the mean new bone 2.1 +/- 1.0 mm. In every case treated with GTR, the formation of new attachment was followed by a varying amount of new bone. After both types of regenerative treatment the newly formed cementum displayed a predominantly cellular character. The findings of the present study indicate that the treatment of intrabony defects with enamel matrix proteins or with bioabsorbable membranes enhances the formation of a new connective tissue attachment in humans.