An assay for computerized scoring of the DNA content of the protozoan Tetrahymena pyriformis has been used for the detection of toxic responses to cocaine, since DNA is responsible for the replication of the genetic material and also reflects closely the number of chromosomes in the nucleus. Thus, doubling of the number of chromosomes in a cell will also correspond to doubling of the DNA content and of the nuclear volume. Two chemical forms of cocaine were used, cocaine hydrochloride and cocaine freebase (crack), at two doses of 1 and 2 mg per 100 ml of protozoan culture, respectively. Image analysis of the protozoan nucleus patterns revealed a rapid stimulating effect on the DNA content for both cocaine hydrochloride and freebase after 1 h of incubation. However, after 2 h of treatment a reduction, although not statistically significant, of the DNA content of the protozoan was observed. These observations were further correlated with the phagocytic activity of the protozoan cultures. This paper provides some possible explanations of the toxic effects of cocaine on this particular cell model.