Between August 1997 and September 1998, 14 cases of hyper-reactive malarial splenomegaly (HMS) were diagnosed in the Instituto de Salud Carlos III in Madrid, Spain. These cases, from Equatorial Guinea and Cameroon, were identified using the diagnostic criteria established by Y. M. Fakunle in 1981: gross splenomegaly; high levels of anti-malarial antibodies; IgM in serum at least two standard deviations above the local mean; and clinical and immunological response to antimalarial treatment. Although malarial parasites were only detected in the Giemsa-stained blood films of four of the cases, these four and four others were found to have the DNA of such parasites in their blood when tested using a method based on a semi-nested, multiplex PCR. These result indicate that malarial parasitaemias may be more prevalent in HMS than is usually recognized.