The statistical distribution of colony counts in the spleen colony assay was determined in C57BL/6 and C3H mice under varying conditions of the assay procedure. Assay mice were given syngeneic bone marrow cells from normal or irradiated donors. The mice were injected intravenously with marrow cells either immediately or 3 days after irradiation. Eight days after engraftment, spleen colonies were counted and the statistical distribution of colony counts was determined using a mean to variance ratio criterion. Analysis of the data indicated that the statistical distribution of colony counts was different in the two strains of mice. In addition, delaying time of injection of mice with bone marrow cells or injecting bone marrow cells form irradiated donors also changed the statistical distribution. The significance of this work lies in the fact that modification of the usual assay procedure can alter the statistical distribution of colony counts, thus changing the statistical accuracy of the assay. Modification in the assay procedure, such that an increase occurs in the variance of the distribution of colony counts, must be compensated for by increasing the number of spleens counted in order to maintain a constant level of statistical accuracy in experiments.