Previous studies suggest that cutaneous and muscle afferents use different environmental cues in growing to their peripheral targets. As a first approach to learning whether these earlier observations reflect differences in the behavior of individual growth cones, trigeminal cutaneous and muscle afferents of embryonic day 10 chicks were cocultured with explants of epidermis or dermis or with myotubes, and interactions of their growth cones with these potential targets were followed with time lapse video microscopy. Cutaneous and muscle afferents differed in their response to all three targets. In birds, few cutaneous afferents innervate epidermis. Accordingly, most cutaneous neurites retracted within minutes of touching an epidermal cell. In contrast, most muscle afferents stopped growing but remained in contact with epidermis for as long as they were observed (> 1 hr). Further, most cutaneous afferents grew readily across explants of dermis, their normal target, at rates comparable to their growth on the substrate. In contrast, most muscle afferents advanced only poorly on dermis. Finally, most cutaneous afferents grew readily across myotubes, the normal targets of muscle afferents. In contrast, few muscle afferents grew across myotubes; most either retracted or changed course and grew along the myotube. Overall, muscle afferents stayed in contact with myotubes longer than cutaneous afferents. These cell-type-specific responses reflect in large part the patterns of cutaneous and muscle afferent growth in vivo. Further studies are required to determine whether these observed differences between the behavior of regenerating cutaneous and muscle afferent growth cones could potentially play a role in the selection of targets or pathways during embryonic development.