Little is known about the direct effect of chemotherapy on normal peripheral blood leukocytes (PBL) or its contribution to leukopenia. We examined 5′-fluorouracil's (5FU) effect on PBL apoptosis and adhesion molecules' expression in a single-drug solid-tumor model. Possible apoptosis mediators were examined. The study included 32 colorectal cancer patients; apoptosis was determined by annexin-V binding and light-scatter morphology before and after drug infusion. CD18, CD11a, CD11b, and CD63 membranal levels were assayed by flow cytometry. Apoptosis was increased post-5FU administration in neutrophils (PMN), monocytes and lymphocytes (P < 0.05). Levels of Fas receptor and activated caspase 3 did not vary indicating that the procces was not mediated by caspase 3 in the timeframe studied. Reduced CD63 on monocytes and decreased CD18 expression on PMN and non-apoptotic monocytes were observed (P ≤ 0.05). CD11a,b expression did not vary. Decreased CD18 and CD63 levels were demonstrated in apoptotic and non-apoptotic PBL implying a more direct association with the drug itself.