This paper describes the results of two endoscopic studies of Naprelan (Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania), a controlled-release formulation of naproxen sodium. In one study, 19 healthy male subjects received either 2 controlled release Naprelan 500-mg tablets once daily or 1 Naprosyn (naproxen; Syntex Laboratories, Inc., Palo Alto, California) 500-mg tablet BID. At baseline, all subjects had gastroduodenal endoscopy scores of 0 on both the Lanza and Euler scales. Although the trend favored Naprelan, differences in Lanza and Euler scale elevations were not statistically significant. Eight of 10 subjects in the Naprelan group and 7 of 9 subjects in the Naprosyn group reported a total of 27 adverse events (AEs). In the second study, healthy subjects received Naprelan 1,000 mg once daily, Naprosyn 500 mg BID, and film-coated aspirin 650 mg QID. In the stomach, there was a significant difference in favor of Naprelan over aspirin (P = 0.0001) and in favor of Naprosyn over aspirin (P = 0.0001). Fewer erosions were seen in the duodenum than in the stomach. In the duodenum, there was a significant difference in favor of Naprelan over Naprosyn (P = 0.0236), and in favor of Naprelan over aspirin (P = 0.0086), but the difference between Naprosyn and aspirin was not significant (P = 0.6643). Of the 23 subjects who received medication, 12 reported AEs: 8 while receiving aspirin, 3 while receiving Naprosyn, and 1 while receiving Naprelan. Differences in the number of erosions and ulcers seen following each of the periods of drug administration favored Naprelan and the Intestinal Protective Drug Absorption System.