The aim of the present study in man was to investigate the influence of cigarette smoking on basal plasma concentrations of neurotensin-like immunoreactivity (p-NTLI), as well as on fat-induced elevation of p-NTLI levels. On three separate occasions, habitual tobacco smokers either ingested fat (55 ml Intralipid 20%) or smoked three cigarettes, or ingested fat and smoked. The subjects were fasted overnight and told no to smoke during the fasting period. Smoking of one cigarette at one hour intervals (0, 60, and 120 min) did not change the p-NTLI levels (n = 6). Ingestion of fat caused a significant increase (n = 16) and when these two procedures were combined (n = 16), the mean integrated p-NTLI response (nM0-180 min) was 56% larger than the response after fat ingestion alone. The results show that cigarette smoking potentiates the fat-induced elevation of p-NTLI levels, whereas cigarette smoking per se has no effect.