The recent discovery of potent, specific, long-acting thromboxane receptor antagonists, like SQ 33,961, mandated that studies be conducted to follow up an earlier study, which showed potential antiulcer activity of the short-acting thromboxane antagonist, SQ 28,668, in the taurocholic acid gastric erosion model in rats. In experiments conducted with the same taurocholic acid protocol, SQ 33,961 caused a dose-related reduction in taurocholate-induced gastric erosions, with an ID50 value of 12 micrograms/kg, i.p. In additional studies, aspirin and indomethacin were shown to produce gastric erosions in rats, and SQ 33,961 also inhibited gastric erosion in response to these anti-inflammatory drugs. The ID50 values were 0.24 and 0.26 mg/kg i.p. vs. aspirin (200 mg/kg, p.o.) and indomethacin (200 mg/kg, s.c.), respectively. The inhibition of aspirin-induced gastric injury by SQ 33,961 was confirmed histologically. This gastroprotective activity was not peculiar to SQ 33,961, because the structurally unrelated thromboxane receptor antagonist, BM 13,505, also significantly inhibited the development of aspirin-induced gastric lesions. In a more severe model, SQ 33,961 (10 mg/kg, i.p.) reduced gastric erosions by only 32% (not significant) 1 hr after ethanol ingestion (1 ml, p.o.) in rats. SQ 33,961 did not inhibit the antiphlogistic activity (carrageenan paw edema assay) of indomethacin, nor did it inhibit the analgesic activity (phenylquinone writhing assay) of aspirin. A dose of SQ 33,961 producing > or = 95% inhibition of nonsteroidal anti-inflammatory drug-induced gastric erosion (10 mg/kg, i.p.) produced a 37% reduction in the volume of gastric secretion without changing the titratable acidity of gastric contents.(ABSTRACT TRUNCATED AT 250 WORDS)