Lake whitefish (Coregonus clupeaformis) from four stocks in northern Lakes Michigan and Huron were collected seasonally from fall 2003 through summer 2006 and examined for the presence of Renibacterium salmoninarum, the causative agent of bacterial kidney disease (BKD), using culture techniques on modified kidney disease medium (MKDM) and the quantitative enzyme-linked immunosorbent assay (Q-ELISA). R. salmoninarum was detected in 62.31% (according to Q-ELISA) of the 1284 examined lake whitefish, with some fish displaying the typical signs of BKD, such as renal congestion, swelling, and whitish nodules. Kidney cultures on MKDM yielded bacteria with morphological and biochemical characteristics identical to those of R. salmoninarum recovered from other Great Lakes fish species, as well as those from other parts of the world. Isolate identification was confirmed via nested polymerase chain reaction. Antibiograms demonstrated high sensitivity to enrofloxacin and ciprofloxacin, sensitivity to oxytetracycline, erythromycin, azithromycin, chloramphenicol, novobiocin, and carbenicillin, and resistance to polymyxin B, clindamycin, and kanamycin. Statistical analysis of R. salmoninarum prevalence and intensities revealed significant interactions among stocks, years and sampling seasons, with highest prevalence generally in fall and frequent wide variation in prevalence and intensity from one season to the next for a particular stock. It was surprising to find that the prevalence of R. salmoninarum exceeded 50% in the four stocks, much higher than originally thought. Moreover, a positive association between R. salmoninarum intensity and the abundance of the swimbladder nematode, Cystidicola farionis, was identified. Our findings suggest that Great Lakes lake whitefish are vulnerable to serious fish pathogens.