Human myelomonocytic leukemic HL60 cells express the CD45 common leukocyte antigen, a tyrosine-phosphatase which is involved in the regulation of chloride channels activated during apoptotic volume decrease (AVD). Low (1mM) concentrations of butyrate induce cell differentiation towards the monocytic lineage within 48h-72h, as assessed by flow-cytometric detection of the monocytic marker CD86. Evaluation of apoptosis as measured by 7AAD nuclear staining/phosphatidylserine exposure, activation of caspases and DNA-fragmentation in cell cycle analysis (flow cytometry; subG1-fraction 4.070.36%, n=6) reveals that the number of apoptotic cells is comparable in treated and untreated cells. Higher concentrations of butyrate (5–10mM) rapidly induce apoptosis within 24–72h (subG1-fraction 29.402.47%, n=6, p=0.05). The increase of caspase+ cells is paralleled by a decrease of CD45- cells. Both caspase+ and caspase- cells which express CD45 exhibit a higher cell volume (CV) and display AVD between 24h and 72h of butyrate treatment. In contrast CD45- cells have a smaller CV and do not display apparent AVD. Hence the presence of CD45 is likely to be involved in AVD. In addition 33.9314.69% (n=6) of 10mM butyrate-treated CD45+ cells show caspase activation and exhibit a strong increase of granularity. In contrast the number of caspase+ cells is significantly higher in the CD45+ fraction (83.863.78%; n=4; p=0.05). However, these cells do not respond with increased granularity upon butyrate treatment. Furthermore, CD45 expression is down regulated by butyrate treatment as assessed by quantitative RT-PCR.