A 36 year old white man was diagnosed as having Whipple's disease after a prolonged illness of lethargy, night sweats, and weight loss associated with lymphadenopathy and splenomegaly. Biopsy specimen of an inguinal lymph node confirmed the presence of periodic acid Schiff positive macrophages and culture gave a pure growth of Corynebacterium jeikeium. Twelve hours after the introduction of oral co-trimoxazole and streptomycin the patient's condition deteriorated. He became confused, feverish, and developed florid retinal vasculitis with associated visual impairment. Both the systemic symptoms and the retinal vasculitis responded to treatment with corticosteroids and his vision returned to normal. We think this was a Jarisch-Herxheimer reaction not previously described in Whipple's disease and advise inspection of the fundi of such patients before starting treatment.