In a series of 56 patients (24 uncomplicated postoperative and 32 septic patients), neopterin and elastase alpha 1 protease inhibitor complex (E-alpha 1 PI) plasma levels were measured daily. The clinical course of each patient was evaluated with the Multiple Organ Failure (MOF) score according to Goris. Neopterin could differentiate between septic and nonseptic patients (p less than .001), and E-alpha 1 PI between septic nonsurvivors and nonseptic patients only (p less than .01). In septic patients, acute pulmonary insufficiency was indicated by elevated E-alpha 1 PI values (greater than or equal to 400 micrograms/L) 1 day before mechanical ventilation was performed with a sensitivity of 81% and a specificity of 82%. Defining a patient with MOF whose score was greater than or equal to 5 as a high-risk septic patient, a comparison neopterin greater than or equal to 40 nmol/L and E-alpha 1 PI greater than or equal to 400 micrograms/L, measured 1 day before the evaluation of an MOF score of greater than or equal to 5 yielded a sensitivity of 91% and a specificity of 99% when patients fulfilled both criteria. We conclude that neopterin and E-alpha 1 PI might be useful parameters for the diagnosis of septicemia and monitoring of the clinical course in septic patients. Moreover, they might indicate the possible central role of macrophage and PMN activation in the development of MOF.