In vertebrates, many responses to stress as well as homeostatic maintenance of basal metabolism are regulated by plasma glucocorticoid hormones (GCs). Despite having crucial functions, levels of GCs are typically variable among individuals. We examined the contribution of several physiological factors to individual variation in plasma corticosterone (CORT) and the number of corticotropin-releasing hormone (CRH) neurons in the magnocellular preoptic area of the brain in free-living Allegheny Mountain dusky salamanders. We addressed three hypotheses: the current-condition hypothesis, the facilitation hypothesis and the trade-off hypothesis. Differential white blood cell count was identified as a strong contributor to individual variation in baseline CORT, stress-induced CORT and the number of CRH neurons. In contrast, we found no relationship between CORT (or CRH) and body condition, energy stores or reproductive investment, providing no support for the current-condition hypothesis or the trade-off hypothesis involving reproduction. Because of the difficulties of interpreting the functional consequences of variation in differential white blood cell counts, we were unable to distinguish between the facilitation hypothesis or the trade-off hypothesis related to immune function. However, the strong association between differential white blood cell count and hypothalamic-pituitary-adrenal/interrenal (HPA/I) activation suggests that a more thorough examination of immune profiles is critical to understanding variation in HPA/I activation.