Longlasting nociceptive stimulation is known to cause atrophy of adjacent muscles. The aim of this study was to determine further the possible mechanisms of this pathological phenomenon. Unilateral fracture of the paw was performed under pentobarbital anaesthesia in several experimental groups (n = 8-11) of female and male rats. Dry muscle weights of the soleus (SOL), extensor digitorum longus (EDL), gastrocnemius (GA) and tibialis anterior (TA) were determined 7 days following the bone fracture and compared to the weight of contralateral control muscles. To demonstrate the reflex origin of this atrophy, deafferentation of the paw by dorsal root section (L4_5) was performed before or after unilateral fracture of hindlimb metatarsal bones. In female rats, the fracture resulted in a significant loss of muscle weight in all the four muscles examined. When the hindlimb was deafferented prior to the fracture, no muscle atrophy developed, and neither did deafferentation itself cause any appreciable change in muscle weight except in male rats. This supports the concept that this type of atrophy is reflex in origin. Deafferentation, when performed after the fracture, did not prevent the weight loss in extensor muscles (SOL, GA), while the flexors (EDL, TA) did not in general lose any weight. The results in male rats had a similar trend as in female rats, although the weight loss was significantly smaller. Our results showed that the mechanism of reflex muscle atrophy following metatarsal bone fracture involves a component which is dependent on afferent information from the injured paw. Differences in the degree of affection of different muscle types (extensors vs flexors, slow vs fast muscles) and of female and male rats suggest that the muscle atrophy is the result of a complex process that probably also involves hormonal mechanisms.