The aim of this study was to investigate pretreatment prognostic factors that could be useful in predicting the response to plasma exchange in thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Thirty-two patients with TTP/HUS, treated with plasma exchange at our institution from 1980 to 1994, were studied. The main clinical and laboratory data at the beginning of plasma exchanges were analyzed by the Cox stepwise logistic regression, applied to either treatment failure or death. Seventeen (53%) patients attained a complete remission and 22 (69%) survived (five in advanced renal failure and long-term hemodialysis). Longer delay in initiating plasma exchanges, presence of stupor or coma, and higher creatinine levels at the beginning of plasma exchanges were independent predictors of treatment failure. Stupor or coma at the beginning of plasma exchanges was the only predictor of mortality from unremitted TTP/HUS. Hemoglobin levels, platelet count, and LDH activity, traditionally envisaged as markers of disease activity, neither correlated with previous duration of TTP/HUS nor had any prognostic value. Early diagnosis of TTP/HUS and prompt initiation of intensive plasma exchange emerged from this study as the most effective interventions for improving the prognosis of TTP/HUS patients.