Item response theory methods were used to study differential item functioning (DIF) between gender groups on a measure of stress reaction. Results revealed that women were more likely to endorse items describing emotional vulnerability and sensitivity, whereas men were more likely to endorse items describing tension, irritability, and being easily upset. Item factor analysis yielded 5 correlated factors, and the DIF analysis, in turn, revealed differential gender mean differences on these factors. This finding illustrates how even in an essentially unidimensional scale, comparison of group mean differences can be affected by multidimensionality caused by item clusters that share similar content. Results do not support arguments that measures of negative affective dispositions “artificially” produce gender mean differences by focusing on specific selected content areas.