1. Acid extracts of muscle-fibre preparations from human biopsies incubated with [U-14C]glucose were chromatographically analysed.
2. Radioactivity of fructose was significantly greater in muscle from childhood dystrophy patients and also in female carriers of the disease compared with normal, foetal, neurogenic muscle disease and polymyositis control groups.
3. Measurements of the activity of polyol-NADP oxidoreductase (EC 184.108.40.206) and L-iditol-NAD oxidoreductase (EC 220.127.116.11) in muscle extracts compared with the ability of extracts to dephosphorylate fructose 6-phosphate, indicated that the probable route of fructose formation from glucose is via glucitol. The mean activities of the two specified enzymes in dystrophic muscle showed 13- and 3–5-fold increases respectively compared with normal muscle, and smaller increases compared with other controls.
4. Direct comparison of labelling patterns following incubation of muscle-fibre preparations with d-[U-14C]glucose, d-[U-14C]fructose and d-[U-14C]glucitol showed that these three substances are rapidly interconvertible mutual major metabolic products, confirming the glucitol pathway as a major route of fructose formation.
5. [U-14C]fructose is readily metabolized by dystrophic muscle, excluding the possibility of its accumulation being the result of poor utilization.
6. Inhibition of polyol oxidoreductase in dystrophic muscle preparations by 3,3′-tetramethyleneglutarate drastically reduces the ability of the fibres to utilize [U-14C]-glucose, and prevents the formation of [14C]fructose.
7. Some implications of these results are discussed in relation to the pathogenesis of childhood muscular dystrophy.