Background: Aberrant crypt foci (ACF) are clusters of morphologically altered crypts which can be observed by light or stereomicroscopy on the mucosal surface of the colon after staining with methylene-blue. They probably represent one of the earliest events in human colorectal carcinogenesis. The main purpose of the present study was to observe the surface features of aberrant and normal colonic crypts in humans using scanning electron microscopy (SEM) in order to find and measure differences between aberrant and normal. Materials and Methods: Fifteen mucosal specimens containing ACF and 8 with normal mucosa taken from patients operated on for colon cancer were observed under a scanning electron microscope. Results: By SEM ACF were easily observed on the mucosal surface because they showed a well defined border and were elevated on the mucosal surface. Under higher magnification luminal openings of aberrant crypts had a larger overall average diameter than normal (37.6 mu m +/- 13.5, mean a SD, vs 15.9 mu m +/- 4.9, P=0.001), though when crypt multiplicity of ACF (number of crypts per ACF) was higher, the diameter of luminal openings tended to be smaller and similar to those of normal crypts, with weak negative correlation between crypt multiplicity of ACF and mean diameter of aberrant luminal openings (r=-0.27). Finally, the mucosal surface among aberrant crypts was flattened because of a loss of microvilli. In conclusion, scanning electron microscopy allows a better definition of the topological features of aberrant crypt foci than light or stereomicroscopy.