This study examined the effect of pyrimethamine (PYR) on sister chromatid exchanges (SCEs) in human lymphocytes. PYR is a folic acid antagonist used for the treatment of malaria and toxoplasmosis. PYR was added to peripheral blood lymphocyte cultures at three different doses: 0.05, 0.1, and 0.2 mg/ml. The results of the cytogenetic and statistical evaluations showed that the frequency of SCEs increased significantly in a dose-dependent manner. Thus, it is shown that PYR has a genotoxic effect on human chromosomes. Teratogenesis Carcinog. Mutagen. 18:163-169, 1998. (C) 1998 Wiley-Liss, Inc.