This report presents histologic results in humans following a laser-assisted new attachment procedure (LANAP) for the treatment of periodontal pockets. Six pairs of single-rooted teeth with moderate to advanced chronic periodontitis associated with subgingival calculus deposits were treated. A bur notch was placed within the pocket at the clinically and radiographically measured apical extent of calculus. All teeth were scaled and root planed with ultrasonic and hand scalers. One of each pair of teeth received treatment of the inner pocket wall with a free-running pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) laser to remove the pocket epithelium, and the test pockets were lased a second time to seal the pocket. After 3 months, all treated teeth were removed en bloc for histologic processing. LANAP-treated teeth exhibited greater probing depth reductions and clinical probing attachment level gains than the control teeth. All LANAP-treated specimens showed new cementum and new connective tissue attachment in and occasionally coronal to the notch, whereas five of the six control teeth had a long junctional epithelium with no evidence of new attachment or regeneration. There was no evidence of any adverse histologic changes around the LANAP specimens. These cases support the concept that LANAP can be associated with cementum-mediated new connective tissue attachment and apparent periodontal regeneration of diseased root surfaces in humans. (Int J Periodontics Restorative Dent 2007;27:577–587.)