Skin lesions, an important clue to the cause of septicemia, result from five main processes: (1) disseminated intravascular coagulation and coagulopathy; (2) direct vascular invasion and occlusion by bacteria or fungi; (3) immune vasculitis and immune complex formation; (4) emboli from endocarditis; and (5) vascular effects of toxins. Disseminated intravascular coagulation probably plays only a minor role in pathogenesis. Vascular invasion by bacteria may result in a severe inflammatory reaction, as in meningococcemia, or in a minimal reaction, as in ecthyma gangrenosum. Gram-stained smears of scrapings from the base of skin lesions--a frequently neglected procedure--is an important diagnostic adjunct. Skin biopsies are particularly important in the diagnosis of Rocky Mountain spotted fever and infections caused by Candida.