study objective: To determine the pathogenesis and clinical course of lactic acidosis in adults receiving standard medical care. design: Placebo arm of a 5-year prospective, randomized, blinded study comparing placebo and dichloroacetate as specific lactate-lowering therapy. Each patient received intravenous saline placebo in addition to conventional therapy. setting: Intensive care units of 10 tertiary care hospitals in North America. patients: One hundred twenty-six patients with lactic acidosis, defined as arterial blood lactate greater than or equal to 5 mmol/L and either arterial pH of less than or equal to 7.35 or base deficit greater than 6mmol/L. Patients were followed for up to 6 months. measurements and main results: Mean ± SD demographic entry data for 126 patients included: age 56 ± 17 years, lactate 10.4 ± 5.5 mmol/L, pH 7.24 ± 0.14, calculated base deficit 14.1 ± 5.4, arterial systolic blood pressure 103 ± 29 mm Hg, Glasgow Coma score 7.9 ± 4.9, and APACHE II score 19.2 ± 8.1. Despite fluids and pressors, 32% of patients had systolic blood pressures of less than or equal to 90 mm Hg in association with sepsis (59%), cardiac failure (18%), or hemorrhage (18%). The most common causes of lactic acidosis in the absence of shock were sepsis (49%), liver disease (15%), and respiratory failure (12%). The median survival was 38.5 hours. Survival at 24 hours was 59%. Arterial pH predicted 24-hour survival better than base deficit or bicarbonate level. Percent survival was 41% at 3 days and 17% at 30 days. Only 21% of patients survived to leave the intensive care unit, and 17% were discharged from the hospital. In patients receiving sodium bicarbonate, neither acid-base nor hemodynamic status improved. conclusions: In this first prospective study of the clinical course of acute lactic acidosis in adults, nearly all subjects had both hemodynamic and nonhemodynamic (metabolic) underlying causes, many of which independently predicted survival and most of which were refractory to standard care. © 1994.