BACKGROUND. Recent NIH statistics indicates that more that 40% of Americans are obese, with more than 20% of these individuals being morbidly obese. Invasive surgical procedures have been considered the most effective and reliable avenue for sustainable long-term weight reduction. However, non-invasive techniques for dynamically achieving volume reduction from inside the stomach are lacking. AIM. The aim of this study was to design temporary, permeable, controllable pseudobezoars for non-invasive but long-term sustainable gastric volume reduction and to test them in pilot chronic animal and human experiments. METHODS. Permeable sac-like carriers made from biocompatible and biodegradable material were filled with expandable absorbent fiber and polymer granules, and the designed implements were packed into standard 000 gelatin capsules. The material of the carrier and the mixture of fiber and polymer granules were optimized for maximal volume expansion in simulated gastric acid environment, for swelling speed and for dimensional hardness to prevent the expulsion of the pseudobezoars through the pylorus. The implements were administered chronically and transorally to 2 dogs (1M, 25.1 kg, 1F, 30.25 kg) and two human volunteers (1M, 78.9 kg/174 cm, BMI 26.06 kg/m2, girth 88.1 cm, and 1M, 89.7 kg/175 cm, BMI 29.29 kg/m2, girth 95.2 cm) according to a predesigned administration schedule. Food intake, body weight and girth dynamics, stools, regularity and notable side effects were monitored in three distinct periods, baseline, therapy, and washout, lasting one month each. RESULTS. The presence of the pseudobezoars in the stomach was confirmed endoscopically in the dogs and sonographically in the humans. Both dogs exhibited a significant reduction of food intake (2-tailed Student t-test, p<0.05), which did not materialize in significant weight reduction probably due to the relatively short therapy period. Significantly increased water intake was noted, and very few side effects were recorded. After an extensive implement optimization for improved controllability and safety, a more vigorous pseudobezoar therapy was administered to the volunteers resulting in significant weight loss and girth reduction during the therapy period, and high satiety scores on the satiety scale of Haber. These effects diminished gradually during the washout period. The subjects did not report any notable discomfort or side effects. CONCLUSION. Controllable temporary pseudobezoars have been designed, optimized and tested in pilot chronic animal and human studies. The results clearly demonstrated the feasibility of this novel alternative approach in obesity management.