Associations between major psychologic stressors and immune function have been documented in previous research, but few studies have investigated immune changes attending minor, normative stressors. This study examined adrenocortical and behavioral predictors of immune responses to starting kindergarten in 39 five-year-old children, who completed laboratory visits for venipunctures 1 wk before (time 1) and 1 wk after (time 2) school entry. At time 1, children were also immunized with pneumococcal vaccine. Immune responses were measured as change scores for T (CD4+ and CD8+) cells, B (CD19+) cells, lymphoproliferative responses to pokeweed mitogen (PWM), and type-specific pneumococcal antibody responses (ABR). Adrenocortical response was assessed as the change in salivary Cortisol level, and behavioral difficulty with school adjustment was scored using parental ratings of behavior problems, stress due to changes in routines, and degree of adaptive challenge. Salivary Cortisol rose after kindergarten entry (means = 0.39 ± 0.28 to 0.49 ± 0.36 µg/dL, p = 0.03) and was unrelated to behavioral difficulties. CD4+ cells increased in number, whereas PWM declined, and CD19+ cells showed a borderline increase. Change in salivary Cortisol was positively associated with change in CD19+ (ΔCD19+) and inversely related to ABR. Scores for behavioral difficulty were inversely associated with ΔCD4+ and ΔCD19+. These data suggest that: 1) school entry is a stressor capable of evoking elevations in Cortisol and behavior problems, accompanied by shifts in functional and enumerative measures of immune status; and 2) children with greater adrenocortical reactivity have increases in B cell numbers and less effective B cell-mediated antibody production, whereas children with more behavioral difficulties show declines in all T and B cell subsets.