Roman high- (RHA) and low-avoidance (RLA) rats have been genetically selected on the basis of their active avoidance behavior, and have been shown to differ on numerous behavioral, neurochemical and neuroendocrine parameters, especially in response to stress. We investigated the activity of splenic lymphocytes in vitro. Natural killer cell activity against YAC-1 tumoral cells and the mitotic response to plant lectins concanavalin A and phytohemagglutinin were much lower for lymphocytes isolated from RHA rats, in males as well as in females. The difference between the two strains was even larger when measured in a stressed state, immediately after active avoidance learning. On the other hand, the mitotic response to bacterial lipopolysaccharide, a B-cell-specific mitogen, was not different between the two lines, indicating that the difference in lymphocyte reactivity is limited to the T-lineage. The lower activity of T-cells in the RHA line had no consequence upon the ability of these animals to build up an antibody response against sheep red blood cells. These results indicate that Roman lines are an interesting animal model for the study of the relationships between the brain and the immune system, as well as for the analysis of the genes involved in the control of behavior.