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The size of cardiac muscle fibers was determined for 15 patients with Down syndrome who did not have congenital heart disease and for 15 age- and sex-matched control patients by counting the number of cardiac muscle cells in specified areas of microscopic sections (method of Black-Schaffer and Turner). Mean ratio of muscle cells per unit area for the Down patients versus controls was 84.9%, with mean cross-sectional area of Down fibers 117.8% of control value and calculated mean volume of Down cells 127.7% of control value. Mean weights of Down hearts related to normal for age, versus control hearts, was 79.8% of control values. Calculated ratio of total cardiac muscle cell number in Down hearts was 62.5% of the value for controls. This value corresponds closely to the 62.4%, which can be calculated from Naeye's data on cardiac muscle fiber size in Down syndrome based on a point-count method, and is also close to published values for liver cell size and number and skeletal muscle nuclear number in Down syndrome. This study demonstrates that the Black-Schaffer and Turner method gives results equivalent to those of the point-count method for studies of cardiac muscle fiber size, and further supports the suggestion that chromosome 21 controls the size and number of at least certain cell types.