The RATIO observatory collects nationwide data on opportunistic infections, severe bacterial infections, and lymphomas in patients with a past or present history of tumor necrosis factor alpha (TNFalpha) antagonist treatment in France. The cases are validated by a committee of experts, and the capture-recapture method is used to check and to improve case ascertainment. A nested case-control comparison is carried out to identify risk factors for the events of interest. The registry differs from other biological registries in that the inclusion criterion is occurrence of the event (infection or lymphoma) instead of administration of the treatment. This method ensures collection of a far larger number of cases. The RATIO observatory is a remarkable example of a three-way partnership of learned societies, pharmaceutical companies, and institutions (the French research institute INSERM and the French drug safety agency AFSSAPS). Over 100 events were reported in the first 16 months, a large increase compared to European registries of fixed patient cohorts monitored for 4-5 years. This result validates our original approach, which will probably need to be extended to other biotherapies for inflammatory joint disease and to other potential adverse events. The strong commitment of rheumatologists in France, who are the main prescribers of TNFalpha antagonists, and of the French Society for Rheumatology explain the high case-ascertainment and must continue to ensure that answers are rapidly provided to the drug safety questions that are vital to our patients.