To determine the contaminants that should be studied further in the subsequent population-based study, a profile of Great Lakes (GL) sport fish contaminant residues were studied in human blood and urine specimens from 32 sport fish consumers from three Great Lakes: Lake Michigan (n = 10), Lake Huron (n = 11), and Lake Erie (n = 11). Serum was analyzed for 8 polychlorinated dioxin congeners, 10 polychlorinated furan congeners, 4 coplanar and 32 other polychlorinated biphenyl (PCB) congeners, and 11 persistent chlorinated pesticides. Whole blood was analyzed for mercury and lead. Urine samples were analyzed for 10 nonpersistent pesticides (or their metabolites) and 5 metals. One individual was excluded from statistical analysis because of an unusual exposure to selected analytes. Overall, the sample (n = 31) consumed, on average, 49 GL sport fish meals per year for a mean of 33 years. On average, the general population in the GL basin consume 6 meals of GL sport fish per year. The mean tissue levels of most persistent, bioaccumulative compounds also found in GL sport fish ranged from less than a twofold increase to that of PCB 126, which was eight times the selected background levels found in the general population. The overall mean total toxic equivalent for dioxins, furans, and coplanar PCBs were greater than selected background levels in the general population (dioxins, 1.8 times; furans, 2.4 times; and coplanar PCBs, 9.6 times). The nonpersistent pesticides and most metals were not identified in unusual concentrations. A contaminant pattern among lake subgroups was evident. Lake Erie sport fish consumers had consistently lower contaminant concentrations than consumers of sport fish from Lake Michigan and Huron. These interlake differences are consistent with contaminant patterns seen in sport fish tissue from the respective lakes; GL sport fish consumption was the most likely explanation for observed contaminant levels among this sample. Frequent consumers of sport fish proved to be effective sentinels for identifying sport fish contaminants of concern. In the larger study to follow, serum samples will be tested for PCBs (congener specific and coplanar), DDE, dioxin, and furans.