The effect of histamine and cimetidine on the growth of four human colon cancer cell lines was studied. Histamine significantly stimulated the uptake of tritiated thymidine in vitro in a dose dependent manner, to a maximum of 120% and 116% of controls for C170 and LIM2412, respectively. This effect was antagonised by cimetidine, but not diphenhydramine. Histamine also stimulated a dose dependent increase in cyclic adenosine monophosphate accumulation in C170 cells, antagonised by cimetidine. When grown as subcutaneous xenografts in Balb/c nu/nu mice, cimetidine had a significant inhibitory effect on the same two cell lines. The final volume of C170 tumours in animals given cimetidine was 44% of controls. This response was dose dependent, plateauing at a cimetidine dose of 50 mg/kg/day. The final volume of LIM2412 tumours in animals given cimetidine was 60% of controls. Histamine administered locally by a mini-osmotic pump stimulated C170 tumour growth to 164% of controls, was antagonised by cimetidine at a dose of 200 mg/kg/day, but not by lower concentrations. Histamine has a trophic effect on at least two colorectal cancer cell lines in vivo and in vitro. As this effect is antagonised by cimetidine, it may be mediated via tumour histamine type 2 receptors.