Environmental indicators in the Zahuapan-Atoyac hydrological system (ZA:HS) in Tlaxcala, Mexico, a region impacted by wastewater discharges from urban, agricultural and industrial sources, were assessed. Samples were collected in the spring 2008 dry season. Sixteen sampling stations were selected, stretching from the source of the Zahuapan River, including three samples from the Atoyac River, to its exit point from the state of Tlaxcala. Arsenic, lead, pH and temperature were measured in the water samples; in the sediments, the following were measured: arsenic, lead, texture, organic matter content, total organic carbon, pH and electrical conductivity according to NMX-AA-051-SCFI-2001, Goyberg-Rein and Vázquez, 2003 and NOM-021-SEMARNAT-2000. The results showed that the arsenic concentrations ranged from 0.06 to 0.87 mg•L-1 in water and from 1.3 to 127 mg•kg-1 in sediment, whereas lead levels reached up to 1.05 mg•L-1 in water from a place called El Ojito and 89.5 mg•L-1 in sediment from the Apizaco station. These levels exceeded the national and international levels set for drinking water and protection of aquatic life. The results suggest an anthropogenic contribution at some stations that adds to natural pollution.