We report a case of sero-negative tsutsugamushi disease diagnosed by polymerase chain reaction (PCR). A 54-year-old man who worked in Nagano prefecture presented with flu-like symptoms that did not respond to cephalosporin therapy. On admission to another hospital, chest roentgenography revealed abnormal shadows; liver dysfunction was also present. Despite therapy, the patient's condition gradually worsened and he was transferred to our intensive care unit. Erythema on all extremities and scabs on the right medial femoral region and the dorsum of the left foot suggested a diagnosis of tsutsugamushi disease. We administered minocycline and gave percutaneous cardiopulmonary support for adult respiratory distress syndrome. Despite all efforts, the patient died. Although serologic tests were not positive, Karp strains of R. tsutsugamuschi were identified on PCR amplification. Autopsy revealed evidence of acute hemorrhagic pancreatitis, which has not been reported previously in tsutsugamushi disease. We conclude that PCR techniques may be useful in confirming a diagnosis of early tsutsugamushi disease.