Four new knotting techniques were developed for use at flexible endoscopy: (1) half hitches tied with knot-pusher, (2) thread-locking device, (3) self-tightening slip-knot, and (4) externally releasable knot. Remoteness from site of action, access through small-diameter orifice, and difficulty in applying lateral traction to tighten knots are problems met in knot tying at endoscopy. All four knotting techniques were studied in experiments on postmortem human stomachs and used for radio-telemetry studies and anti-reflux operations in survival studies in dogs using endoscopic sewing techniques. Half hitches tied at endoscopy with a knot-pusher were also used in human studies to treat esophageal reflux and secure pH radio-telemetry capsules for long-term measurements. Externally releasable knots were used to secure nasogastric tubes to the stomach of five patients for long-term nutrition. Knot tying is feasible at flexible endoscopy by a variety of new techniques. Endoscopically tied knots can be as secure as surgically hand-tied knots and have been used successfully in man.