<i>Background/Aims:</i> Neonatal stress induces permanent physiological changes that may influence the immune system. Early-life stress increases asthma disease severity in children. We investigated the effects of early-life stress on allergic airway inflammation using a murine model of asthma coupled to maternal separation as an early-life stress stimulus. <i>Methods:</i> Maternally separated (MS) and unseparated control (CON) mice were sensitized with ovalbumin (OVA) beginning at day 31 after birth. <i>Results:</i> Challenging mice with OVA increased airway hyperresponsiveness (AHR) and the number of inflammatory cells recovered in the bronchoalveolar lavage (BAL), compared to saline-challenged mice. Challenging MS mice with OVA resulted in less total inflammatory cells, eosinophils, interferon-γ, and interleukin-4 in BAL compared to CON mice. However, MS mice challenged with OVA exhibited AHR similar to CON mice challenged with OVA. In contrast, an enhanced stress protocol (MS+) involving removal of pups from their home cages following the removal of the dam resulted in inflammatory cell accumulation and cytokine levels in the BAL similar to CON mice and higher than MS mice. <i>Conclusions:</i> These findings indicate that the effect of early-life psychological factors on the development of airway inflammatory diseases such as asthma is very complex and depends on the quality of the psychological stress stimulus.