Lassa fever is widespread in West Africa, where the case fatality is about 16% in hospitalized adult patients. The clinical course is highly variable, with a few patients developing severe disease with bleeding, adult respiratory distress syndrome, encephalopathy and hypovolemic shock. We studied 70 patients admitted with suspected Lassa fever to a hospital in Sierra Leone, West Africa. Fourteen patients classified as having severe Lassa fever on the basis of serum aspartate amino transferase (AST) greater than 150 IU/L or viremia of greater than 10(3.6) tissue culture infective dose (TCID) 50/ml were found to have statistically significantly depressed lymphocyte counts when compared with patients with mild Lassa fever (AST less than 150 IU/L or viremia, less than 10(3.6)TCID50/ml), (P less than 0.0001) and with febrile control patients, in whom Lassa infection had been excluded by laboratory criteria (P less than 0.0008). Maximum depression occurred a mean of 10.9 days post onset. Patients with severe Lassa fever also had moderate thrombocytopenia, which was statistically significant when compared with febrile control patients (P less than 0.0003) and this occurred a mean of 10.8 days postonset. The most significant changes were in platelet function, which was markedly depressed in patients with severe Lassa fever (P less than 0.0035 in response to ADP and P = 0.0081 for collagen) when compared with patients with mild Lassa fever, and when compared with febrile controls, (P = 0.0013 for ADP and P less than 0.00001 for collagen). This abnormality was usually maximal on admission to hospital, and probably is an early event, preceding hospitalization in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)