We evaluated the effect of sulindac sulfide (SS), which reduces cell number and induces apoptosis in cultured colon cancer cells (CCCs), on expression of the proliferation markers PCNA and Ki-67 in HT-29 and HCT-15 CCCs; only the former express cyclooxygenases. DNA content and PCNA/Ki-67 expression were analyzed by bivariate flow cytometry. SS inhibited cell proliferation, determined by the reduced expression of PCNA and Ki-67, roughly by half at 72 h, and induced apoptosis (accounting for about two-thirds and one-third of the reduction in cell number, respectively). A similar effect of SS occurred in HT-29 and HCT-15 CCCs, and also in non-colonic cells, indicating that this rather general effect of SS on cultured cells is not dependent on inhibition of prostaglandin synthesis. (C) 1997 Elsevier Science Ireland Ltd.