In previous cytogenetic studies of rabbits injected with the clastogen, streptonigrin (SN), we observed a higher incidence of chromosome aberrations in lymph node cells than in marrow cells recovered 6 h after treatment. In this study we examined several factors that may be responsible for this difference in the incidence of lesions. Results from SN pulse-treated lymphoid and marrow cultures demonstrated that the responses were different in vitro also. In addition, at higher doses of SN, lymphoid cells displayed a greater sensitivity to the drug when treated during DNA synthesis; marrow cells showed no differences in sensitivity throughout the cell cycle. Analysis of the percentage of lymph node and marrow metaphases labeled following 2, 4, or 6 h of culture in the presence of tritiated thymidine indicated that G2 was less than 2 h in lymph node cells and approximately 4 h in marrow cells. From these data we conclude that the difference in the length of G2 in the two cell types is partially responsible for the difference in the incidence of lesions 6 h after an in vivo SN exposure. However, our data also indicate that lymph node cells are innately more sensitive to the induction of lesions than are marrow cells.