In order to explore whether an organ-specific pattern in cytokine and lactate concentrations exists in patients with multiple organ failure (MOF), we measured the cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha), and lactate in blood taken from the hepatic vein, pulmonary capillaries, and peripheral veins of 10 patients with MOF with hepatic involvement (MOF-HI), eight patients with MOF and adult respiratory distress syndrome (MOF-ARDS), and five head-injured patients (controls). Ten additional patients participated in a study of arteriovenous pulmonary concentration gradients of these substances. For statistical analysis, nonparametric tests and analysis of variance (ANOVA) were used. The regional concentrations of these substances exhibited a different pattern in the two MOF groups. In the MOF-HI group, mean +/- SD cytokines IL-1beta and IL-6 (pg/ml) were respectively 216 +/- 100 and 461 +/- 343 in the hepatic sinusoidal blood; 149 +/- 52 and 293 +/- 204 in pulmonary capillary blood; and 148 +/- 105 and 234 +/- 162 in peripheral venous blood. In the MOF-ARDS group the corresponding levels were 180 +/- 103 and 235 +/- 124; 235 +/- 94 and 280 +/- 108; and 130 +/- 77 and 194 +/- 127. The TNF-alpha levels also exhibited the same pattern. The mean +/- SD corresponding levels (mmol/L) for lactate in the MOF-HI group were 3.1 +/- 1.8, 1.5 +/- 0.3, and 1.2 +/- 0.6, and in the MOF-ARDS group were 1.1 +/- 0.9, 1.8 +/- 1.1, and 1.0 +/- 0.2, respectively. The differences in the levels of all substances between the liver and lungs in the two MOF groups were statistically significant (p < 0.003). In the study of transpulmonary gradients it was shown that the levels of cytokine and lactate were lower in arterial blood than in mixed venous blood in MOF-HI patients, whereas the opposite was true in MOF-ARDS patients. In this study, we found that in MOF, cytokines and lactate are secreted from the most severely affected organs.