Based on our previous studies that aspirin (ASA) -induced gastric ulceration in rats can be significantly reduced if the drug is chemically associated with phosphatidylcholine (PC), we undertook the present study to compare gastric ulcer healing rates in rats administered either unmodified or PC-complexed ASA. Gastric ulcers were induced in anesthetized rats by briefly exposing the mucosal surface to 0.2 ml 60% acetic acid followed by randomization of the rats to study groups; daily intragastrically administered saline (control), ASA (36, 54 mg/kg), or ASA-PC complex. In contrast to the 65-70% reduction in ulcer size recorded in controls, ulcer healing was significantly retarded in rats administered unmodified ASA. Conversely, the size of the experimentally induced ulcers was less than control values in rats daily administered the PC-associated ASA, suggesting an acceleration in the rate of ulcer healing. Daily intragastric administration of ASA to rats over the study period also resulted in a significant decrease in surface hydrophobicity from control values as measured by contact angle analysis. However, surface hydrophobicity was partially restored in rats administered the PC-complexed ASA. Consistent with these findings, it was determined that ASA-treated rats had a lower hematocrit than control values, as an index of gastrointestinal bleeding, whereas this parameter remained at control levels in rats administered the PC-complexed ASA. We conclude that PC-associated ASA promotes ulcer healing above the values measured in rats treated with ASA or saline. This property may be attributable to the fact that in contrast to unmodified ASA, which aggravates ulcer healing by transforming the stomach to an acid-permeable state, the protective hydrophobic lining of the stomach is maintained in rats administered PC-associated ASA, thereby allowing ulcer healing of the tissue to proceed.