RATIONALE: Severe respiratory syncytial virus (RSV) infection is associated with asthma but the nature of this association is imperfectly understood. OBJECTIVES: To examine the nature of the association between severe RSV infection and asthma in a population-based sample of twins. METHODS: Data on hospitalization due to RSV infection was gathered for all twins born in Denmark between 1994 and 2000 (8,280 pairs) and linked to information on asthma obtained from hospital discharge registries and parent-completed questionnaires. Genetic variance components models and direction of causation models were fitted to the observed data. MEASUREMENTS AND MAIN RESULTS: RSV hospitalization and asthma were positively associated (r = 0.43), and genetic determinants for the two disorders overlapped completely. Modeling the direction of causation between RSV hospitalization and asthma showed that a model in which asthma "causes" RSV hospitalization fitted the data significantly better (P = 0.39 for deterioration in model fit) than a model in which RSV hospitalization "causes" asthma (P < 0.001 for deterioration in model fit), even when sex, birth weight, and maternal smoking during pregnancy were accounted for. CONCLUSIONS: RSV infection that is severe enough to warrant hospitalization does not cause asthma but is an indicator of the genetic predisposition to asthma.