The multisib (MS) sampling strategy was used for detecting possible genetic influences on a complex and heterogeneous disorder. The MS strategy increases the likelihood of selecting pedigrees for single genetic factors and allows the efficient analysis of data. The collection of complete pedigrees will procure additional data, but at a large marginal expense. The MS ascertainment procedure was applied to seizure disorders by examination of taurine excretion levels and by conducting two-dimensional gel electrophoresis of plasma proteins. Reduced taurine excretion (propsed to be genetically controlled) was found to associate with seizures, particularly in those individuals with a generalized spike and wave (GSW) EEG, or in families with a GSW-seizure history. Examination of two-dimensional gels showed hypohaptoglobinemia in several seizure patients [Panter et al, 1984]. The frequency of hypohaptoglobinemia is greatly increased in familial seizure cases, and may also be genetically controlled. Thus the MS strategy has proven successful in identifying kindreds in which specific physiological alterations may contribute toward the complex phenotype of seizures.