Trichloroacetic acid (TCAA), a known mouse liver carcinogen and a possible human carcinogen, is found in chlorinated drinking water. We measured TCAA in archived urine samples from a reference population of 402 adults using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry. TCAA was detected in 76% of the samples examined at concentrations ranging from < 0.5 micro g TCAA/L to more than 25 micro g/L; the 90th percentile concentration was 23 micro g/L (22 micro g TCAA/g creatinine); and the geometric mean and median concentrations were 2.9 micro g/L (2.6 micro g/g creatinine) and 3.3 micro g/L (3.2 micro g/g creatinine), respectively. The frequency of detection of TCAA in urban areas was higher than in rural areas (p = 0.00007), and sex and place of residence (i.e., urban vs. rural) were found to have a significant interaction in modulating the levels of TCAA (p = 0.012). Urban residents had higher mean levels of TCAA (men, 5.3 micro g/L, 3.8 micro g/g creatinine; women, 2.9 micro g/L, 2.8 micro g/g creatinine) than did rural residents (men, 2.2 micro g/L, 1.7 micro g/g creatinine; women, 2.6 micro g/L, 2.7 micro g/g creatinine). The higher frequency of detection of TCAA in urban than in rural areas and higher levels of TCAA among urban than among rural residents may reflect the fact that urban residents use primarily chlorinated water from public water supplies, whereas those in rural areas are more likely to obtain water from private wells, which typically are not chlorinated.