Several experimental studies have demonstrated that granulocytes have an important role in causing the necrosis of ischemic tissue by capillary plugging and superoxide radical formation. Adenosine is spontaneously released by ischemic cells and inhibits the granulocytic superoxide radical formation. 5-Aminoimidazole-4-carboxamide riboside, a naturally occurring by-product in purine biosynthesis, stimulates the release of ischemic cell adenosine and indirectly blocks the granulocyte-induced tissue necrosis. 5-Aminoimidazole-4-carboxamide riboside (10-500 mg/kg) was administered intraperitoneally in a blinded fashion once (single dose, 30 minutes before surgery) or twice (double dose, 30 minutes before and 5.5 hours after surgery) in groups of rats. The controls received intraperitoneal saline solution in the same fashion. Each rat underwent the elevation of a caudally based random skin flap. The flap viability was determined in a blinded fashion on the seventh post-operative day and statistically compared by Fisher's exact test. When 300 or 500 mg/kg of 5-aminoimidazole-4-carboxamide riboside was given as a single dose, the mean percentage of rat skin flap necrosis (19.4% +/- 3.1% and 19.6% +/- 4.2%, respectively) was lower but not significantly different from that of the control group of rats (29.3% +/- 2.7%) (p less than 0.08). Additionally, two doses of 500 mg/kg of 5-aminoimidazole-4-carboxamide riboside yielded a mean percentage of rat skin flap necrosis (12.24% +/- 4.58%) much lower (21.68% +/- 3.18%) than that of the control group of rats (p = 0.056). Our blinded fashion study demonstrated an almost statistically significant reduction of random skin flap distal necrosis after intraperitoneal injection of high doses of 5-aminoimidazole-4-carboxamide riboside.(ABSTRACT TRUNCATED AT 250 WORDS)