A method for culturing mixtures of allogeneic mouse spleen cells which gives quantitative results is described. The kinetics of the response is reproducible from experiment to experiment and the dose-response curve is linear. Radiation survival studies indicate that the responding cells require the capacity to proliferate during the mixed-leukocyte reaction (D37 = 95 rads). From experiments with the spleen cells of congenic resistant strains it is evident that the response is controlled by minor histocompatibility loci as well as by the H-2 locus.