Most studies employing bioelectrical impedance analysis (BIA) for estimating appendicular skeletal muscle mass using descriptive BIA models rely on statistical rather than biophysical principles. The aim of the present study was to evaluate the feasibility of estimating arm and leg muscle volume (MV) based on multiple bioimpedance measurements and using a recently proposed mathematical model and to compare this technique to conventional segmental BIA at high and low frequencies. MV of the arm and leg, respectively, was determined in 15 young, healthy, active men [age 22 ± 2 (SD) yr, total body fat 15.6 ± 5.1%] by magnetic resonance imaging (MRI) and BIA using a conventional and new bioimpedance model. MRI-determined MV for leg and arm was 6,268 ± 1,099 and 1,173 ± 172 cm3, respectively. Estimated MV by the new BIA model [leg: 6,294 ± 1,155 cm3 (50 kHz), 6,278 ± 1,103 cm3 (500 kHz); arm: 1,216 ± 172 cm3 (50 kHz), 1,155 ± 157 cm3 (500 kHz)] was not statistically different from MRI-determined MV (leg: P= 0.958; arm: P= 0.188). The new BIA model was superior to conventional BIA and performed best at 500 kHz for estimating leg MV as indicated by the lower relative total error [new: 3.6% (500 kHz), 5.2% (50 kHz); conventional: 7.6% (500 kHz) and 8.3% (50 kHz)]. In contrast, the new BIA model, both at 50 and 500 kHz, did not improve the accuracy for estimating arm MV [new: 10.8% (500 kHz), 10.6% (50 kHz); conventional: 11.8% (500 kHz), 11.4% (50 kHz)]. It was concluded that modeling of multiple BIA measurements has advantages for the determination of lower limb muscle volume in healthy, active adult men.