Small cell lung cancer (SCLC) cells express cholinergic nicotinic receptors on their membranes, and the stimulatory effect on cell growth of nicotine has been described in cell cultures. We investigated three SCLC cell lines, all showing high levels of fluorescence intensity when labeled with FITC alpha-bungarotoxin in most cells. From one of these cell lines, NCI-N592 a tumor line in athymic nude mice was established. Nude mice were subcutaneously grafted on the same day with tumor fragments and with Alzet osmotic minipumps (200 microliters, 14 days of infusion) infused with serotonin or nicotine to investigate their effects on tumor growth. Two dose levels of each compound were used, namely 20 and 200 micrograms/day. In mice treated with 200 micrograms serotonin, tumors took a shorter time than those of untreated controls to reach 50 mg in volume, meaning that the first steps of tumor growth were faster. In contrast, a delay in tumor appearance was observed in mice treated with low-dose serotonin. No differences were found in tumor growth in the groups of mice treated with nicotine. When the treatment was delivered to already established and vascularized tumors (around 100 mm3), no effect on tumor growth was achieved by serotonin or nicotine. Therefore, in the experimental conditions used in the study, the stimulatory effect of nicotine on an SCLC tumor was not demonstrated.