Flare-ups of fibrodysplasia ossificans progressiva are most commonly triggered by soft tissue trauma. After observing severe flare-ups of fibrodysplasia ossificans progressiva in two half-sisters with culture-confirmed influenza B infections, we hypothesized that influenza-like viral illnesses also can trigger fibrodysplasia ossificans progressiva flare-ups. To address this hypothesis, we designed a questionnaire to assess whether patients with fibrodysplasia ossificans progressiva experienced influenza symptoms during the 2000 to 2001 influenza season, and whether these symptoms were correlated with flare-ups of the condition. The questionnaire was sent to patients with fibrodysplasia ossificans progressiva worldwide. Of the 264 patients surveyed, 123 (47%) responded. The survey revealed that the risk of a disease flare-up of fibrodysplasia ossificans progressiva during an influenza-like viral illness was increased at least threefold and possibly much more. The survey data strongly supported the hypothesis that influenza-like viral illnesses are associated with disease flare-ups in patients who have fibrodysplasia ossificans progressiva. Influenza-like viral illnesses may be a source of previously unrecognized muscle injury leading to heterotopic ossification and permanent loss of mobility in these patients. These findings have important implications for understanding and preventing environmental triggers of disease activity in this population of patients genetically susceptible to progressive heterotopic ossification.