['Weight-loss attempts are likely to become more frequent as the prevalence of obesity rises. Repeated cycles of loss and gain are a common consequence of failed weight-loss attempts. The question of whether this pattern has negative health effects is unresolved. The objective of this research was to investigate associations between weight-loss history and current measures of immune function.', 'The study design was a cross-sectional study.', 'One hundred fourteen healthy, overweight, sedentary, postmenopausal women were recruited for an exercise intervention study and were currently weight stable.', 'History of intentional weight loss was assessed by questionnaire. Flow cytometry was used to measure natural killer cell (NK) cytotoxicity at four effector-to-target (E:T) ratios and for enumerating and phenotyping lymphocytes. Multiple linear regression analysis was used to investigate associations between weight loss within the past 20 years and current immune function.', 'Women who reported ever intentionally losing >or=10 pounds had lower measured NK cytotoxicity than those who did not (24.7%+/-12.1% vs 31.1%+/-14.7%, respectively, at E:T 25:1; P=.01). Increasing frequency of previous intentional weight loss was associated with lower NK cytotoxicity (P=.003, trend). As an independent predictor, longer duration of recent weight stability was associated with higher NK cytotoxicity (21.6%+/-11.9%, 24.4%+/-11.0%, and 31.9%+/-14.4% for <or=2, >2 to <or=5, and >5 years of weight stability, respectively; P=.0002, trend). The frequency of weight loss episodes was also associated with differences in the number and proportion of NK cells.'] Is frequent intentional weight loss associated with lower natural killer cell cytotoxicity in postmenopausal women : possible long-term immune effects?