The mechanisms of recovery of manual dexterity after unilateral lesion of the sensorimotor cortex in adult primates remain a matter of debate. It has been proposed that the cortical zone adjacent to the lesion may take over part of the function of the damaged cortex. To investigate further this possibility, two adult (4-5 years old) macaque monkeys were trained to perform a natural precision-grip task to assess hand dexterity. Intracortical microstimulations (ICMS) were used to map the hand area in M1 on both hemispheres. Ibotenic acid was then injected intracortically to damage the representation in M1 of the preferred hand. Subsequent histological analysis indicated that the hand representation in M1 was indeed lesioned, but, due to a spread of ibotenic acid, the lesion encroached a significant extent of the hand representation in the primary somatosensory cortex. A few minutes after infusion of ibotenic acid, there was a complete loss of dexterity of the preferred hand, which lasted for 1-2 months. Later, a progressive functional recovery of the affected hand took place over a 3- to 4-month period, reaching a stable level corresponding to 30% of the pre-lesion behavioral score. ICMS remapping, conducted nine months after the lesion, revealed that stimulation of the intact or lesioned M1 did not induce any visible movement of the recovered hand. The M1 hand representation on the intact hemisphere was similar to that observed before the lesion. Transient inactivation of the M1 hand/arm areas or of the dorsal and ventral premotor cortical areas (PM) on both hemispheres was undertaken by using microinjections of the GABA-agonist muscimol. Inactivations of M1 had no effect. Inhibition of PM in the damaged hemisphere suppressed the recovered manual dexterity of the affected hand. These results suggest that PM plays a significant role in the incomplete functional recovery of hand dexterity following unilateral damage of the sensorimotor cortex in adult monkeys.