The appetite and weight regulating peptide leptin was associated recently with alcohol craving during withdrawal. Nevertheless, correlations were only significant with craving displayed on the visual analogue scale for maximum craving during the previous week (VAS), and not if assessed with the highly validated Obsessive Compulsive Drinking Scale (OCDS). The objective of the following study, therefore, is to elucidate further the associations between the leptin system and craving concepts during alcohol withdrawal. A sufficiently large sample size should allow multiple statistical subgroup and confounder analyses. We prospectively investigated 102 chronic alcoholic inpatients (23 females, 79 males) during withdrawal on days 0 (admission), 1, 2 and days 7-10. In addition to the statistical analysis of the total sample, females and males were to be analysed separately. For detecting associations between leptin levels and craving scores multiple regression analysis was performed. Plasma leptin levels were determined, and craving for ethanol was assessed by both the OCDS and the VAS. Leptin plasma levels significantly increased during alcohol withdrawal compared to day 0, while all craving scores decreased. Body mass corrected leptin plasma levels predicted craving on day 0 in the OCDS total score (R=0.55, F=7.91, df=1.19, p<0.05) and in the OCDS obsessive subscore (R=0.57, F>=8.48, df=1.19, p<0.05) in females. Neither in males nor in the total population did multiple regression analysis reveal any significant results. Leptin levels seem to change during inpatient alcohol withdrawal. In a multivariate model, correlations between leptin levels and the highly validated craving scores of the OCDS can only be assumed in females. Hence, gender differences have to be taken into account when searching for neurobiological models of alcohol craving.