Hyperreactive Malarial Splenomegaly Syndrome (HMSS) was described and defined before sensitive tests for malaria were available. We present a series of seven individuals who were referred to our clinics with possible HMSS. Chronic malaria was demonstrated in those successfully treated but not in those who failed to respond to therapy. This observation suggests that the newer molecular malaria assays have a role to play in the identification of individuals who are likely to respond to treatment for HMSS in non-endemic regions.