: Emtricitabine is structurally similar to lamivudine, which has been associated with red cell aplasia. We describe four patients with severe anaemia presenting soon after starting emtricitabine-containing antiretroviral therapy. Bone marrow biopsy in three patients confirmed red cell aplasia. Anaemia resolved after emtricitabine withdrawal in three patients, one patient died, and anaemia recurred on rechallenge in one patient whose anaemia persisted on lamivudine, resolving when this was stopped, suggesting a possible cross-reaction between lamivudine and emtricitabine.