In India, natural preparations derived from the plants are widely use for the treatments of various diseases. Hence, it becomes necessary to assess the modulating action of the plant extract when associated with other substances. Potassium canrenoate (PC) is a synthetic steroid and is used in the treatment of hypertension. It is not only a genotoxic agent, but also a tumor-initiating agent. In the present study, the effect of various doses (i.e., 5, 10, 20, and 30 mu M) of PC were studied for their genotoxic effects in the presence of S9 mix in cultured human lymphocytes, using mitotic index, chromosomal aberrations, sister chromatid exchanges, and replication index as parameters. PC was found to be genotoxic at 20 and 30 mu M. Treatment of 30 mu M of PC was given along with different doses of Plumbago zeylanica extract (i.e., 107.5, 212.5, 315, and 417 mu g/mL) of the culture medium. A dose-dependent decrease in the genotoxic effects of PC was observed. The result suggested that the plant extract per se does not have genotoxic potential, but can modulate the genotoxicity of PC in cultured human lymphocytes.