In a field study, DNA damage, hematological parameters, and liver somatic index were measured in fish collected from freshwater creeks contaminated with polychlorinated biphenyls (PCBs) and polyaromatic hydrocarbons (PAHs) (East Tennessee) and from estuarine and marine waters contaminated with PAHs and cadmium (Mississippi Sound). For comparison, specimens were examined from two pristine reference sites near the impacted Tennessee and Mississippi sites. Significantly more strand-breaks were found in DNA isolated from liver tissue of redbreast sunfish (Lepomis auritus) from contaminated creeks than in DNA from sunfish from two pristine creeks. Hemoglobin concentration (C(Hb)) and mean corpuscular hemoglobin concentration (MCHC) were significantly higher in both male and female sunfish from the pristine creeks. Furthermore, the liver somatic index (LSI) of sunfish from contaminated creeks was higher than that of specimens from reference sites. In adult male, female, and juvenile hardhead catfish (Arius felis) from suspected contaminated sites in the Mississippi Sound, high LSI and lowered C(Hb) and MCHC were found A higher percentage of double-stranded DNA was measured in specimens from the pristine reference sites. Individual differences in responses of the biological markers, however, were large, as reflected by high standard deviations. The biological responses measured were obviously valuable to indicate differences in the environmental quality expressed in molecular and physiological terms.