<jats:title>Abstract</jats:title><jats:p>Nimbolide, a triterpenoid extracted from the flowers of the neem tree (<jats:italic>Azadirachta indica</jats:italic>), was found to have antiproliferative activity against some cancer cell lines. Treatment of cells with 0.5–5.0 μ<jats:sc>m</jats:sc> concentrations of nimbolide resulted in moderate to very strong growth inhibition in U937, HL‐60, THP1 and B16 cell lines. Flow cytometric analysis of U937 cells showed that nimbolide treatment (1–2.5 μ<jats:sc>m</jats:sc>) resulted in cell cycle disruption by decreasing the number of cells in G0/G1 phase, with initial increases in S and G2/M phases. Cells exposed to a higher dose of nimbolide for a longer period displayed a severely damaged DNA profile, resulting in a remarkable increase in the number of cells in the sub‐G1 fraction, with a reciprocal decrease of cells in all phases. Quantification of the expression of phosphatidylserine in the outer cell membrane showed that doses of nimbolide higher than 0.4 μ<jats:sc>m</jats:sc> exerted remarkable lethality, with over 60% of cells exhibiting apoptotic features after exposure to 1.2 μ<jats:sc>m</jats:sc> nimbolide. The antiproliferative effect of nimbolide and its apoptosis‐inducing property raise hope for its use in anticancer therapy by enhancing the effectiveness of cell cycle disruption. Copyright © 2006 John Wiley & Sons, Ltd.