We have previously reported on our findings of aberrant crypts (AC) in the colons of rodents treated with a colon carcinogen. In this report, the specificity of AC formation was assessed by testing a variety of agents for their ability to induce AC in the colons of CF1 and C57BL/6J mice. In addition, the ability of each of the agents to induce nuclear aberrations (NA) was assessed and compared with the AC data. The test agents included hydrazines, polycyclic aromatic hydrocarbons, aromatic amines, and nitrosocompounds. The colons were assessed for AC 2 or 4 weeks following a single treatment with the test agent. Of the seven agents that induced AC formation, five were colon carcinogens and the other two were agents believed to be carcinogenic to organs other than the colon. None of the five agents believed to be noncarcinogens induced AC whereas three of them did induce NA in at least one of the strains of mice tested. Comparison of AC and NA induction for each test agent showed that all agents that induced AC also induced NA and that the converse was not true. The findings of the present study indicate that AC are induced specifically in response to colon carcinogens and support our contention that AC are preneoplastic lesions.