This study explored prospectively the effects of dispositional and situational optimism on mood (N = 90) and immune changes (N = 50) among law students in their first semester of study. Optimism was associated with better mood, higher numbers of helper T cells, and higher natural killer cell cytotoxicity. Avoidance coping partially accounted for the relationship between optimism and mood. Among the immune parameters, mood partially accounted for the optimism-helper T cell relationship, and perceived stress partially accounted for the optimism-cytotoxicity relationship. Individual differences in expectancies, appraisal, and mood may be important in understanding psychological and immune responses to stress.