Objective We studied whether suppressed secretion of the orexigenic peptide ghrelin might be involved in the anorexigenic effects of nicotine. Methods Fifty healthy non-smokers chewed gums containing 2 mg nicotine, or no nicotine in a double-blind randomised crossover design in two independent studies. Results Plasma nonacylated ghrelin was not significantly affected by nicotine after 30 and 60 min. Increased blood pressure and decreased appetite ratings confirmed a biological nicotine effect. Conclusions These results do not support a key role of peripheral ghrelin secretion in weight changes related to smoking or smoking cessation, but do not rule out that central nervous system ghrelin is involved.