Although increased morbidity and mortality have been reliably associated with social isolation and less satisfying personal relationships, relatively little is known about the underlying biopsychosocial mechanisms. We assessed problem-solving behaviors and changes in immune function in 90 newlywed couples who were admitted to a hospital research unit for 24 hours. Subjects who exhibited more negative or hostile behaviors during a 30-minute discussion of marital problems showed greater decrements over 24 hours relative to low negative subjects on four functional immunological assays (natural killer cell lysis, blastogenic response to two mitogens, and the proliferative response to a monoclonal antibody to the T3 receptor), as well as larger increases in the numbers of total T lymphocytes and helper T lymphocytes. High negative subjects had higher antibody titers to latent Epstein-Barr virus than low negative subjects, consistent with down-regulated immune function. Women were more likely to show negative immunological changes than men. The discussion of marital problems also led to larger increases in blood pressure that remained elevated longer in high negative subjects than low negative subjects. Positive or supportive problem-solving behaviors were not related to either immunological or blood pressure changes. These physiological differences were particularly noteworthy because marital satisfaction was high in both groups, and couples had been selected on the basis of stringent mental and physical health criteria. These data provide additional support for the link between personal relationships and immune function.