The aim of this study was to determine ifselective inhibition of cyclooxygenase isozymes affectsthe initiation of carcinogen-induced colon cancer usingaberrant crypt foci (ACF) as a surrogate biomarker. Male Sprague-Dawley rats (18 per group) weregiven single subcutaneous injections of saline (4ml/kg), aspirin (50 mg/kg body wt) sodium salicylate (50mg/kg), indomethacin (4 mg/kg), nabumetone (100 mg/kg), or 16,16-dimethyl-prostaglandin E2(50 mg/kg) for three days. On day 4, 12 rats per groupwere given a subcutaneous injection 2 of1,2-dimethylhydrazine (12 mg base/kg body wt) and sixrats per group received vehicle alone (4 ml/kg) every week for eightweeks, after which drug treatment ceased. Control andsix carcinogen-treated rats per group were killed atthis time and the remaining six rats per group killed 22 weeks later. Colons were scored for ACFnumber and size. Only aspirin caused a significantreduction in total ACF and ACF formation at the earlytime point, but at the later time, there were nosignificant differences between groups. ACF from alltreatment groups increased in size at similar rates atboth time points. Thus, only aspirin demonstrated asignificant, although reversible, suppression ofcarcinogen-induced ACF. Possible mechanisms of action and theclinical implications of aspirin chemoprevention arediscussed.