Thermally hydrolyzed tilapia skin gelatin demonstrated noticeable free-radical scavenging and inhibition of lipid peroxidation. Five factors in production of retorted skin gelatin hydrolysate (RSGH) were screened using a fractional factorial design to identify critical factors. Phosphoric acid concentration, water/skin ratio, and retorting time had significant effects on alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) scavenging by RSGHs. A face-centered, central composite design in these three factors was used to collect data that resulted in strong response surface models of DPPH scavenging (R(2) = 0.977) and inhibition of lipid peroxidation (R(2) = 0.967). The most effective condition resulted in 80.3% DPPH scavenging and 75.0% inhibition of lipid peroxidation. The models were used to predict maxima for the two properties. These were 79.4% for DPPH scavenging activity and 77.3% for lipid peroxidation inhibition. Antioxidative tilapia RSCH has potential as a natural antioxidant because a large amount of low-priced skin by-products can be obtained from the tilapia filleting industry. (C) 2009 Elsevier Ltd. All rights reserved.