We measured levels of virus in sequential specimens from 137 patients with Lassa fever. The probability of fatal disease increased significantly with the level of viremia measured either on admission or during the course of illness. The odds ratio of death in patients with viremia greater than 10 TCID50/ml was 3.7 (90% confidence interval, 1.9-7.2). The same ratio in patients with viremia greater than 10 TCID50/ml and with levels of aspartate aminotransferase greater than or equal to 150 IU/liter was 21.5 (95% confidence interval, 5.2-99.0). Virus was found in throat cultures from 39% of viremic patients, compared with 14% of nonviremic patients (P less than .002); however, the level of virus was usually less than or equal to TCID50/ml. Fewer than 3% of patients were viruric during acute illness, and virus was isolated from three of three samples of cerebrospinal fluid. On admission, 53% of patients had IgG antibodies, and 67% had IgM antibodies. Recovery was not associated with the presence of either IgG or IgM. Virus was isolated from greater than 100 serum specimens that also contained high titers of IgG. Clinical Lassa fever was shown to be a disseminated systemic, primary viral infection, with an outcome highly associated with viremia but not with development of antibody.