BACKGROUND: Over 90% of all cases of malaria worldwide occur in Africa. Current methods of diagnosis are time and labor intensive, and could lead to delayed treatment. METHODS: In this study we investigated the effectiveness of measurements of spleen, liver, and optic nerve sheath diameter (ONSD) in identifying patients with malaria or severe malaria through the use of hand-held ultrasound devices. We recruited 40 adult patients with malaria and 16 adult control subjects at two hospitals in Mwanza, Tanzania. Ultrasonographic diagnosis was compared with rapid antigen diagnostic test and peripheral blood smear as the gold standards. An receiver operating characteristic curve test was performed to determine the most optimal diagnostic threshold for malaria and severe malaria, using each of the measurements for liver size, spleen size, and ONSD. The thresholds were determined to be >12 cm for spleen length and >15.1 cm for liver length, whereas ONSD was not significant in this study. RESULTS: The sensitivities for malaria diagnosis were 66.7% and 58.3% for liver and spleen length respectively, suggesting that these measurements may not be suitable for identifying patients with severe malaria. However, the high specificity of 90.9% for spleen length and the acceptable specificity of 75.0% for liver length suggest that these measurements can be used as a method to eliminate false-positive diagnoses (i.e. patients who do not have severe malaria but are classified as having it by a test with a high sensitivity), giving a high positive predictive value. CONCLUSIONS: We report a high specificity for spleen size and a moderate specificity for liver size in the ultrasonographic diagnosis of severe malaria. Thus when paired with a highly sensitive method of malaria diagnosis, ultrasonographic measurement of spleen and liver size is promising as part of a diagnostic algorithm for malaria. It could be used to stratify risk in patients diagnosed with malaria and assist in their triage. If no sensitive tests are available, ultrasound might be useful to suggest malaria as a cause of a patient's constellation of clinical symptoms.