Conventional approaches to virus detection fail to provide convincing evidence in support of a viral aetiology for SIDS. Virus positivity of about 20% in cases of SIDS is typical of most studies and is similar to that found in control groups. The application of direct immunofluorescence assays (DFA) has increased virus detection rates to 30-40%. Constraints imposed by technology, postmortem interval, choice of samples for analysis and the necessary limitation of virus types to be sought may all result in under-diagnosis of virus positivity. Alpha interferon (IFN alpha), produced by cells in an early response to exposure to many viruses, has been shown to increase in concentration in the cerebrospinal fluid of patients with viral meningitis. In cases of SIDS significant increases in IFN alpha concentrations have been shown in nasopharyngeal aspirates from virus positive cases and from apparently virus negative cases. The application of conventional techniques of DFA and IFN alpha measurement therefore identifies a much larger percentage of SIDS cases as having been exposed to virus. Disturbance of respiratory regulation has been suggested as an aetiological mechanism in SIDS. Apnoeic episodes are frequently described and are known to be associated with certain viral infections, particularly respiratory syncytial virus. The abnormal presence of IFN alpha in neurones of the medulla of the brain stem in a proportion of SIDS cases were identified by immunohistochemistry. This might suggest a link between viral infection and disturbance of respiratory regulation. The higher rates of virus exposure which can now be detected and the localisation of IFN-alpha in medullary neurones suggest that it is premature to discount the viral hypothesis as an explanation for at least a proportion of SIDS cases.