Modulation of tumor blood flow could be of clinical importance, especially when it is combined with radio- or chemotherapy. Serotonin (5-HT), a naturally occurring agent, selectively reduces tumor blood flow and consecutively inhibits the growth of many animal tumors. Therefore, we introduce a new preparation that allows the study of topically applied 5-HT (10(-8) to 10(-2) mol/l) in the microcirculation of a human colon adenocarcinoma. This tumor has been xenotransplanted subcutaneously under the dorsal surface of the ear in athymic nude mice. 5-HT was also tested in the normal skin. The microvascular diameters of large and small arterioles (A1-3) and venules (V1-4) as well as capillaries were measured via closed-circuit videomicroscopy. Normal skin arterioles and venules constricted at higher doses (> 10(-7) mol/l) of 5-HT. In human colon carcinoma, doses of 5-HT higher than 10(-7) mol/l caused constriction of these microvessels; yet, tumor arterioles constricted more than skin arterioles. Thus, 5-HT could selectively reduce blood flow of human colon adenocarcinoma. Based on these findings, we suggest that 5-HT can inhibit growth of human tumors by selectively constricting tumor arterioles.