Cholesteryl butyrate solid lipid nanoparticles (chol-but SLN) have been proposed as a pro-drug to deliver butyric acid. We compared the effects on cell growth, cell-cycle distribution and c-myc expression of chol-but SLN and sodium butyrate (Na-but) in the human leukemic cell lines Jurkat, U937 and HL-60. In all the cell lines 0.5 and 1.0 mM chol-but SLN provoked a complete block of cell growth. Cell-cycle analysis demonstrated in Jurkat cells that 0.25 mM chol-but SLN caused a pronounced increase of G2/M cells and a decrease of G0/G1 cells, whereas in U937 and HL-60 cells chol-but SLN led to a dose-dependent increase of G0/G1 cells, with a decrease of G2/M cells. In Jurkat and HL-60 cells 0.5 mM chol-but SLN induced a significant increase of sub-G0/G1 apoptotic cells. Cell growth and cell-cycle distribution were unaffected by the same concentrations of Na-but. A concentration of 0.25 mM chol-but SLN was able to cause a rapid and transient down-regulation of c-myc expression in all the cell lines, whereas 1 mM Na-but caused a slight reduction of c-myc expression only in U937 cells. The results show how chol-but SLN affects the proliferation pattern of both myeloid and lymphoid cells to an extent greater than the natural butyrate.