The objectives of the series of experiments described were (a) to determine whether there was a circadian rhythm in the incorporation of tritiated thymidine into DNA of the spleen in mice kept on a conventional light-dark cycle and fed ad libitum, (b) to study the effect that different light-dark cycles and a time-limited feeding schedule had on this circadian rhythm, (c) to ascertain what effect the presence of an 8-day Ehrlich ascites carcinoma (EAC) had on the rhythm in DNA synthesis in the spleen and what effect the EAC had on the circadian rhythm in the mitotic index in the corneal epithelium, and (d) to determine whether there was a circadian rhythm in the duration of life-span in mice bearing the EAC. A circadian rhythm in the incorporation of tritiated thymidine into DNA of the mouse spleen consistently was characterized by a peak during the nocturnal phase and a trough during the diurnal phase of the 12-hr light-12-hr dark cycle. In animals bearing an 8-day EAC, the rhythm in DNA synthesis in the spleen was phase-shifted, its wave form was changed, and the overall 24-hr mean was increased significantly. The phasing of the rhythm in EAC-bearing mice was not reproducible. This finding demonstrated that the presence of the EAC severely altered the natural rhythm in DNA synthesis in the spleen and resulted in a rhythmic pattern which was constantly changing. The presence of an 8-day EAC, however, had no effect on the amplitude, overall level, or the phasing of the circadian rhythm in the mitotic index in the cornea. A staggered light-dark cycle of 2 weeks duration did not completely phase-shift the DNA synthesis rhythm in the spleen but did completely phase-shift the rhythm in the mitotic index in the corneal epithelium. In mice subjected to a daily feeding period limited to 4 hr, the rhythm in DNA synthesis in the spleen, in both EAC-bearing and non-EAC bearing mice, was phase-shifted such that the peak occurred during the time of feeding and the trough occurred prior to the feeding period. The rhythm in the mitotic index in the cornea was not phase-shifted or altered in any way by the feeding schedule and thus remained fixed to the light-dark cycle. The DNA synthesis rhythm in the normal spleen demonstrated a phasing very similar to the circadian rhythm in the length of survival in mice challenged with EAC and the circadian rhythm in DNA synthesis in the normal thymus.