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Thirty years ago, in his presentation "The Natural History of Rheumatic Fever," Dr. T. Duckett Jones said, "It has become the order of the day to consider that both the morbidity and the mortality in rheumatic fever have decreased to such an extent as to relegate the problem to a position of unimportance. " He added, "One may wonder, and reach almost any desired conclusion, about what modifying role, if any, the biological characteristics of the streptococci may have played in the reputedly changing pattern. Others may prefer to ponder about the host factors, such as the effect of improved nutrition, improved housing, or other environmental advances. We know of no convincing study which removes these matters from conjecture."' Rheumatic fever is a challenge to physicians and scientists. Attempts to meet this challenge have brought forth new ideas regarding the clinical manifestations, epidemiology, pathogenesis, and control of this disease. Yet, despite the recognized decline in the incidence of rheumatic heart disease in the western world, it remains a serious health problem to children and young adults in developing countries. Why? Although there is no simple answer to this question, it is clear that research in rheumatic heart disease must continue. As expressed by T. Duckett Jones, "The exact incidence of the disease, or the decrease in incidence or severity, seems of less importance than the need to gain further knowledge ofhow and why human beings develop rheumatic fever."' In this presentation I will summarize our knowledge in one area of the pathogenesis of rheumatic fever. I will also dwell on the search for host determinants of

The search for host determinants of susceptibility to rheumatic fever: the missing link. T. Duckett Jones Memorial Lecture.