Information on the structure of human monocytopoiesis was derived from the chronologies of labeled monocytes entering the blood following injection of 3H-thymidine (3H-TDR) and 3H-diisopropylfluorophosphate (3H-DFP). It was found that monocytes are released into the blood directly from a proliferating precursor pool. The marrow cell egress was almost completely restricted to G1-phase monocytes. The egress rate increased with maturation time of promonocytes. The majority of the cells was released at maturation times between 50 and 60 hr. Under normal conditions promonocytes underwent a mean of two catenated cell cycles. The cell cycle time averaged 29 hr and DNA-synthesis time 10 hr. Direct investigations of the promonocytes demonstrated that the medullary promonocyte pool averages 6 x 108 cells/kg body weight in healthy adults. This pool produces a mean of 7 x 106 cells/kg-hr. Proliferation capacity of promonocytes is only partially utilized in normal monocytopoiesis. Induction of acute inflammatory reactions gave rise to an immediate enhancement of promonocyte proliferation activity, thus affording short-term adaptation of monocyte production to monocyte demand. Increase in monocyte production was associated with a shift of marrow release in favor of immature cells.