In order to determine the optimal day for the evaluation of an experimental model of GvHD in F1 mice and the histopathologic evolution of the lesions in different organs, we studied 10-day-old F1 (CBA/J x C57BL/6) mice inoculated with splenic lymphoid cells of the male parental CBA/J strain (n = 42) that were sacrificed between 1 and 14 days postinoculation. The evolution of the relative spleen index (RSI) and the histopathologic lesions in different organs were also determined. F1 mice inoculated with Medium 199 were used as controls. Significant RSI increases (p < 0.0001) were found in the experimental group between 2 and 14 days postinoculation, with a peak at the eighth day, associated with the most severe histopathologic lesions in the organs studied. We suggest the eighth day as the optimal time for evaluation of this experimental model.