Monocytes, defined as peroxidase positive mononuclear cells in the peripheral blood of healthy rats, were labeled by frequent intermittent injections of tritiated thymidine. About 25 per cent of the monocytes were labeled within 1 day and 82 per cent in 8 days. Both labeled and unlabeled monocytes disappeared from the circulation in accordance with an exponential function with a half-time of about 3 days. Mean grain counts increased asymptotically toward a limit reached in 4 or 5 days. The monocyte turnover rate in the rat is in the neighbourhood of 3.6 x 106 cells per day.
It is concluded that monocytes leave the circulation at random and not as a consequence of senescence. It is probable that they are the product of a cell lineage consisting of about 3 generations from the primitive precursor to the mature form, and that the average generation time is about 24 hours. Because of the rapid appearance of large numbers of labeled cells, it is unlikely that they are derived from lymphocytes which acquire label much more slowly.