The early proliferative response previously demonstrated in rabbits has now been shown to follow the mixing of spleen cell suspensions from 2 inbred strains of mice or rats. The size of the response is comparable to that seen in cells from hyperimmune animals exposed to antigen in vitro. Autoradiographs of cells from stimulated cultures showed 1 to 4 per cent of the total population had incorporated thymidine. Modifications in the conditions necessary for the culture of mice and rat spleen cell suspensions and the measurement of thymidine incorporation are described. No responses were observed in isologous mixes. The responses obtained on mixing individual pairs of spleens from different strains showed relatively little variation. Responses were obtained in all of the 21 possible combinations between 7 inbred strains of mice. Responses were obtained when parental cells were mixed with their F1 hybrids. Analysis of these responses showed that, in every case, parental-F1 hybrid responses were less intense than those between the 2 parents. It was shown that there was no inherent defect in the ability of the hybrid cells to respond when mixed with an unrelated strain. The results suggested that the hybrid cells made no response to the parent cells although this was not conclusively established. This has been taken as circumstantial evidence that the response is immunological in nature. The significance of the vigor of the response and the large fraction of the immunologically competent cells that take part is discussed.