We investigated the effect of intrapenile injection of muscle-derived cells (MDC) on the erectile function in rats with bilateral cavernous nerve injury. Rat MDC were harvested and transduced with a retrovirus expressing the lacZ gene. Hanks' balanced salt solution (HBSS) (20 microl) or MDC (1 x 10(6) cells/side) were injected in each corpora cavernosa immediately before bilateral cavernous nerve transection. Intracavernous pressures (ICP) were measured 2 or 4 weeks after surgery with electrical stimulation of the pelvic nerves. Mean maximal ICP of sham group was significantly lower than that of control group both at 2 and 4 weeks after surgery. When MDC were injected into the penis, ICP improved over the sham-injected group at both 2 and 4 weeks after surgery. Percent area of PGP 9.5 staining was significantly greater in MDC-injected penis than in sham-injected at 2 and 4 weeks. Penile MDC injection can facilitate recovery of injured penile innervation and improve erectile function.