We have recently demonstrated that selective breeding of ICR mice for differences in social behavior (i.e., high versus low levels of social isolation-induced aggression) are related to increased susceptibility to tumor development and reduced levels of natural killer (NK) cell activity. In the present investigation, we sought to extend examination of the line differences in immune status to T and B cell responsiveness. In addition, we also sought to determine if social experience contributes to line differences in immune responsiveness. A cosibial design was used to examine whether single vs group housing modified the magnitude of line differences in immune status. Compared to aggressive (NC900) mice, nonaggressive (NC100) mice had significantly lower T cell proliferative responses to concanavalin A, lower IL-2 and gamma-interferon production, as well as significantly lower NK activity. Of the various measures of cellular immune responsiveness, housing condition was found to have a significant effect only on NK activity. No significant line by housing interactions were found for any of the immune measures tested. The present data demonstrate that the genetic selection for differences in social behavior is associated with line differences in several parameters of cellular immune responsiveness. These mouse lines provide a valuable research model to examine the association between selection for genetic differences in social behavior and differences in immune responsiveness.