Cultured skin fibroblasts were obtained from 11 children with lactic acidemia and neurological disturbances. The residual activities of pyruvate dehydrogenase complex were 9 to 45% of control values in all specimens. Immunoblot analysis of mitochondrial proteins using polyclonal antibodies against the alpha and beta subunits of the first component (E₁) of the pyruvate dehydrogenase complex revealed markedly decreased amounts of cross‐reacting material in 4 boys who died in infancy. Two of the boys were half brothers related through a common mother. A fifth boy had an alteration of the electrophoretic mobility of the E₁α subunit and normal E₁β subunit abundance. The remaining 6 patients (2 boys and 4 girls) had normal findings on Western blot assay, and all 11 patients had normal E₂ and E₃ patterns. These findings suggest that the E₁α subunit gene represents a genetically vulnerable site on the X chromosome. Decreased abundance of E₁ components appears to be associated with death in infancy. A normal Western blot analysis is compatible with long‐term survival despite decreased catalytic activity of the pyruvate dehydrogenase complex.