Summary Sprague-Dawley rats were given eight weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH) or of vehicle then were sacrificed at 1, 5 or 24 weeks after the last injection of DMH. The locations of pre-existing aggregates of lymphoid nodules (ALNs), the location and multiplicity (size) of aberrant crypt foci (ACF), and the locations of tumours in the colon were determined. A trimodal distribution of pre-existing ALNs along the length of the colon was significantly correlated with the timodal distribution of DMH-induced adenocarcinomas (ACs ALNs are normal features in the colon of rats that have not been exposed to a colon carcinogen and are consistently found at three distinct sites along the length of the colon of Sprague-Dawley rats (Nauss et al., 1984;Hardman and Cameron, 1994). Solitary lymphoid nodules are rarely observed outside the limits of one of these three sites of ALNs in the rat colon. This unique anatomical distribution of lymphoid nodules in the rat allows study of the role of the lymphoid nodules on colorectal carcinogenesis which is not possible in species in which individual lymphoid nodules are more uniformly distributed in the colon.The findings from several reports (Nauss et al., 1984;Martin et al., 1986;Shamsuddin and Hogan, 1984;Bland and Britton, 1984) have indicated that the majority of carcinogeninduced ACs in the colon of rats occur in close spatial association with each ALN site. In addition, it has been reported that a large proportion of these ACs originate as microscopic, endophytic AC within the ALN . Furthermore, the microscopic, endophytic ACs found within the ALNs showed no evidence of an adenomatous precursor, suggesting that these endophytic ACs arose de novo . It was concluded that ALNs are promotional to development of microscopic, endophytic ACs in the rat and to development of ACs in general.In a recent report addressing the hypothesis that ACF are carcinogen-induced premalignant lesions in the colon of rats (Caderni et al., 1995), the authors examined morphological parameters and mucin production in ACF of whole colons from carcinogen-treated rats to assess the putative premalignant potential of the ACF. The authors found no statistically significant association between either the number of ACF or the size of ACF and the presence of tumours in the colon.The authors did find an association between the presence of a tumour, the number of very large ACF (> 14 aberrant crypts per focus) and the presence of sialomucin-producing ACF.These reports indicate that there may be at least two distinct pathways to carcinogen-induced AC development in the rat colon: one a de novo pathway progressing via the microscope, endophytic lesion associated with the ALN and another pathway progressing via the ACF lesion. It seems reasonable to suggest that if ACF are the main primary early precursor lesions on the pathway to AC formation, then the distribution of ACF along the colon would correlate with the distribution of the ACs. To test this possibility, the distribution of ACF ...