OBJECTIVE: To observe the in vivo effect of combined iontophoresis and laurocapram pretreatment on transdermal delivery of diclofenac sodium gel. METHODS: Diclofenac sodium gel was prepared using polyvinyl alcohol, carboxymethylcellulose sodium and hydroxypropylmethyl cellulose. The diclofenac blood level in rabbits was measured in four groups: passive diffusion, laurocapram pretreatment, iontophoresis (current density controlled at 0.3 mA/cm(2)) and combined laurocapram pretreatment and iontophoresis. Rabbit stratum corneum of each of the four groups was examined using a scanning electron microscope. RESULTS: Diclofenac blood concentration in the passive diffusion group was undetectable. The diclofenac blood concentration area under the curve compared with time was 8.4 &mgr;l ml(-1) h(-1) in the laurocapram pretreatment group, 2.7 &mgr;l ml(-1) h(-1) in the iontophoresis group and 15.4 &mgr;l ml(-1) h(-1) in the combination group. There was no detectable damage observed by scanning electron microscopyto the stratum corneum after iontophoresis or laurocapram pretreatment. CONCLUSION: The combination of iontophoresis and laurocapram pretreatment appears to enhance transdermal delivery of diclofenac sodium gel wi thout significant skin damage.