Regional droughts have far-reaching, substantial, and easily recognizable impacts on populations and the environment. One component of these impacts that is not widely recognized is impairment of immune function by drought-related physiological stress. We studied cell-mediated immune function of cavity-nestling Western Bluebirds (Sialia mexicana), Ash-throated Flycatchers (Myiarchus cinerascens), and Violet– green Swallows (Tachycineta thalassina) at Los Alamos, New Mexico. There was a dramatic decrease in the cell-mediated immune responsiveness of developing nestlings associated with unusually dry conditions. Adult Western Bluebirds captured in 2002 weighed 7% less than in all previous years and average clutch size for all three species was reduced by 21% in 2002. Nestling body mass was also reduced for flycatcher and bluebird nestlings in 2002 compared to all other years. Survival to fledging age was lower overall during the drought years of 2000–2002 compared to the first 3 years of the study.