Abstract As a result of improved LD50/LD90 rates, acceleration of marrow and peripheral neutrophil recovery, and diminished acute toxicity, IL-1 when used with chemotherapeutic agents is said to spare hematopoietic stem cells. However, the impact on, or ability to spare the most primitive hematopoietic stem cell (PHSC) has not been studied to any great degree. Using the competitive repopulation assay, we examined the effect of IL1 with CTX on PHSC function, computing repopulating units (RU): RU = (%) (# of 105 competitor cells used)/(100 − %), where % is percentage donor cell type. C57B6/J (B6) mice, 8–12 weeks old, were injected with 1 μg IL1-α, subcutaneously, 20 hours before administration of 200 mg/kg CTX intravenously; or with CTX alone; IL1 alone; or no drug (control). Four biweekly doses were given and mice were sacrificed 4–6 weeks later. Their marrow (BM) cells were mixed with equal numbers (106 each) of competitor (B6-HbbdGpi1a) cells; equal aliquots of this mixture were injected into lethally-irradiated B6 recipients. The number of mice in each group ranged from 8 to 21, with experiments repeated three times. At 150 days, the percentages of B6 BM were: control 49 ± 3; IL1 only, 66 ± 4; CTX, 32 ± 2; IL1/CTX, 22 ± 3. Differences were significant between control and CTX or IL1/CTX groups (p < 0.001; and between groups receiving IL1/CTX and CTX (p < 0.05). Absolute RU numbers and concentration respectively were: control, 596/11; IL1, 1239/23; CTX, 353/5; IL1-CTX, 195/3. These results indicate that IL1 use with CTX does not lead to PHSC sparing, but rather causes significant further quantitative and qualitative defect in the stem cell population. The previously reported animal sparing may result therefore from effects on organ systems other than the hematopoietic.