BACKGROUND Iatrogenic tumor implantation within surgical sites can compromise curative cancer surgery. Cancer cell adhesion to extracellular matrix proteins is mediated by diverse matrix receptors, most notably integrins. Divalent cations may modulate integrin-ligand interactions in some cells. METHODS We studied adhesion of SW620 and Caco-2 human colon cancer cells to collagen I, the dominant collagen of the interstitial matrix, and confirmed our results in primary human colon cancer cells from surgical specimens. Single cell suspensions in either HEPES/NaCl buffer or media supplemented with 0-1 mM Mn2+ or Mg2+, and 0-10 mM Zn2+ or Ca2+ were plated onto collagen-I-precoated dishes for 30 min. RESULTS Supplementation of the HEPES/NaCl/BSA buffer with 1 mM Mn2+, Mg2+, Zn2+, or Ca2+ affected adhesion differently. Mn2+ (1 mM) markedly promoted SW620 adhesion vs control (21.17 +/- 0.08-fold). Mg2+ (1 mM) had a similar but lesser effect (14.71 +/- 0.02-fold). However, 1-10 mM Ca2+ inhibited basal cell adhesion by 22.0 +/- 3.1 to 88.0 +/- 7.3 % inhibition. Ca2+ (2.5-10 mM) also inhibited Mn2+-induced adhesion. Zn2+ stimulated basal adhesion slightly at lower concentrations but inhibited Mn2+-stimulated adhesion similarly to Ca2+ at higher concentrations. Results were duplicated in conventional serum containing culture medium supplemented with these cations. Caco-2 cells and primary cancer cells yielded similar results. All results are significant to P < 0.01. CONCLUSIONS Integrin-mediated colon cancer cell adhesion is affected by extracellular divalent cation concentrations. Washing the surgical site with dilute calcium or zinc solutions might diminish perioperative tumor implantation.