Concentrated drinking water extracts prepared by adsorption onto XAD-2 resin have been tested for their ability to induce chromosome damage in mammalian cells. Extracts prepared from drinking waters derived from upland and lowland sources have been found to induce chromosome aberrations in Chinese hamster ovary (CHO) cells and human lymphocytes in vitro. Although the identity of the compounds responsible for this activity is unknown, they are generated when the water is chlorinated and appear to bind readily to exogenous protein. When groups of mice were dosed orally with a concentrated water extract, however, no evidence of clastogenic activity in bone marrow cells was apparent. The absence of an in vivo effect may indicate that the mutagenic compounds failed to reach the bone marrow. The possibility that genetic damage could be induced in the cells first encountered in the body after ingestion (i.e., cells in the esophagus, stomach, and intestinal tract) is not precluded by this result. The relevance of these findings in evaluating the potential health hazard of mutagenic compounds in drinking water is discussed.