We have consistently shown that the organoselenium compound 1,4–phenylenebis(methylene)selenocyanate (p-XSC) is a superior cancer chemopreventive agent and less toxic than selenite or certain naturally-occurring selenoamino acids. To elucidate the effects ofp-XSC on human colonic mucosa, biopsies from endoscopically normal sigmoid colon of 30 patients with adenomatous polyps were incubated withp-XSC at concentrations of 1, 2 and 5 μmol/l dissolved in dimethylsulphoxide (DMSO). Biopsies incubated with DMSO or pure culture medium served as a control. Proliferating cells were labelled by bromodeoxyuridine immunohistochemistry and the labelling index (LI) was computed. Upper crypt labelling index (LI of crypt compartments 4+5) and Φh value, which are both discriminators of the expansion of the proliferative zone, were significantly lower after incubation with 1 and 5 μmol/lp-XSC, respectively (LI 4+5: 0.8 and 1.0; Φh value: 2.1 and 2.4), as compared with DMSO (LI 4+5: 3.6 and 4.5; Φh value: 7.0 and 8.3) or culture medium (LI 4+5: 3.3 and 4.5; Φh value: 7.2 and 8.1) (P<0.005 andP<0.05 by Friedman's block test). A trend towards lower levels of LI 4+5 (P=0.059) and Φh value (P=0.075) were seen after 2 μmol/lp-XSC incubation compared with DMSO. Since hyperproliferation of colonic crypt cells with expansion of the proliferative zone is regarded as a biomarker of increased cancer risk, the antiproliferative effects ofp-XSC especially on upper crypt LI and Φh value may indicate a possible protective effect of this organoselenium compound in the prevention of human colon cancer development.