Muscle size is often reported as a single anatomical cross-sectional area (ACSA), rather than volume measured with contiguous MRI scans. However, a single ACSA may provide an inadequate estimate of muscle mass. Therefore, we investigated whether quadriceps muscle volume can be adequately estimated from a single ACSA. In 18 adult males we derived regression equations from which estimates of volume were made. These equations were based on the direct assessment of volume using 11 transverse-plane MRI scans along the entire length of the femur (the gold standard). We estimated volume based on single scans at 40, 50 and 60% of femur length (from the distal end). All estimates of quadriceps volumes were highly correlated to the measured volume and demonstrated a low level of error. R (2) = 0.84, 0.93, 0.90 (all P < 0.01), standard error of estimate (SEE) = 26.8 +/- 5.2, 12.5 +/- 5.4 and 9.9 +/- 5.7%, for single scans taken at 40, 50 and 60% of femur length respectively. In comparison, when volume was estimated using multiple MRI scans corresponding to the maximum ACSA of each muscle the estimate was even better [R (2) = 0.95 (P < 0.01) and SEE = 4.5 +/- 2.7%]. Substituting ACSA from a single MRI scan at 60% of femur length into a previously determined regression equation allows for an estimation of muscle volume with a 10% error of estimate.