We examined the phenotypic variation and clinical genetics in nine families with generalized epilepsy with febrile seizures plus (GEFS+). This genetic epilepsy syndrome with heterogeneous phenotypes was hitherto described in only one family. We obtained genealogical information on 799 individuals and conducted detailed evaluation of 272 individuals. Ninety-one individuals had a history of seizures and 63 had epilepsy consistent with the GEFS+ syndrome. Epilepsy phenotypes were febrile seizures (FS) in 31, febrile seizures plus (FS+) in 15, FS+ with other seizure types (atonic, myoclonic, absence, or complex partial) in 8, and myoclonic-astatic epilepsy in 9 individuals. Inheritance was autosomal dominant with approximately 60% penetrance. This study confirms and expands the spectrum of GEFS+ and provides new insights into the phenotypic relationships and genetics of FS and the generalized epilepsies of childhood. Moreover, the ability to identify large families with this newly recognized common, childhood-onset, generalized genetic epilepsy syndrome suggests that it should be a prime target for attempts to identify genes relevant to FS and generalized epilepsy.