Various forms of status spongiosus occur in neonatal cattle, the best characterized of which is due to mutations of the branched-chain alpha-keto acid dehydrogenase complex (BCKD), resulting in bovine maple syrup urine disease (MSUD, branched-chain ketoaciduria). A distinctive neurological syndrome was identified between 1998 and 2003 in 9 calves in a 250-cow stabilized Gelbvieh-Red Angus herd. Both sexes were affected (6 heifers, 3 bulls), with a low annual incidence (3 cases in 1998; no cases in 1999; 2 cases in 2000; 2 in 2001; 1 in 2002; 1 in 2003). Affected calves were born full-term, unable to stand, and had constant whole-body tremors when stimulated. Animals remained in lateral recumbency until death or euthanasia; the longest survival time was 10 days postpartum. The principal histological change in 2 affected calves was diffuse, moderately severe bilaterally symmetrical status spongiosus with Alzheimer type II cells throughout the white matter of the brain. Myelin deficits were not evident and vacuoles were due to cleaved myelin sheaths. Neither recognized mutation of MSUD was identified in the E1a subunit of BCKD in 2 affected calves, 8 dams that gave birth to affected calves, a grand-dam of 3 affected calves, or a sire of 1 calf. Amino acid analysis of serum from 1 affected calf revealed normal concentrations of branched-chain amino acids, indicating that this disease is distinct from MSUD. The genetic and biochemical basis for the disorder, provisionally named congenital status spongiosus of Gelbvieh-cross cattle, is undetermined. The pattern of inheritance was not established.