The neural drive to a muscle and its biomechanical properties determine the force at a joint. These factors may be centrally linked. We studied the relationship between the ability of first dorsal interosseous muscle (FDI) to generate index flexion force around the metacarpophalangeal joint and the neural drive it receives in a voluntary contraction. The role of FDI was assessed in two thumb postures, thumb 'down' (thumb abducted) and thumb 'up' (thumb extended), and at different thumb carpometacarpal angles. These postures were designed to change acutely the flexion moment arm for FDI. The flexion twitch force evoked by supramaximal stimulation of the ulnar nerve was measured in the two postures and the change in moment arm was assessed by ultrasonography. Subjects also made voluntary flexion contractions of the index finger of ∼5 N in both postures during which neural drive to FDI and the long finger flexor muscles was measured using surface EMG. Recordings of FDI EMG were normalized to the maximal M wave. Five of the 15 subjects also had a radial nerve block to eliminate any co-contraction of the extensor muscles, and extensor muscle EMG was monitored in subjects without radial nerve block. Compared to thumb up, flexion twitch force was ∼60% greater, and the flexion moment arm was ∼50% greater with the thumb down. There was minimal effect of altered carpometacarpal angle on flexion twitch force for either thumb posture. During voluntary flexion contractions, normalized FDI EMG was ∼28% greater with thumb down, compared to thumb up, with no consistent change in neural drive to the long flexors. Hence, the contribution of FDI to index finger flexion can be altered by changes in thumb position. This is linked to changes in neural drive to FDI such that neural drive increases when the mechanical contribution increases, and provides a central mechanism to produce efficient voluntary movements.