C57BL mice were injected intraperitoneally daily with 10 to 50 mg/kg of cocaine for five days. Four hours after the last injection, the thymuses were removed, and the effects on DNA and protein content of the surviving cells were measured. A dose-dependent increase in DNA content per cell, determined by UV spectrophotometric analysis, and a dose-dependent increase in protein content per cell, as measured using the Bio-Rad reagent, were observed. The increase in DNA content per cell was confirmed by H33258 staining of DNA as well as the diphenylamine assay. These changes were also observed when normal thymocytes were cultured with cocaine. Cell cycle analysis by flow cytometry of cocaine-treated cultures revealed the presence of aneuploid cells with increased DNA content. Fewer cells with aneuploidy were observed in experiments with significant apoptosis. Since both aneuploidy and enhanced apoptosis can be induced by cocaine and the amount of aneuploidy cells varies inversely with the degree of apoptosis, we hypothesize that cocaine causes DNA/chromosome damage, which eventually leads to cell death via the apoptosis pathway.