The potential of an anti-inflammatory peptide (antiflammin 1) to reduce irritation when delivered transdermally by iontophoresis was examined. A model drug irritant, chlorpromazine, was co-delivered with and without antiflammin 1 by iontophoresis to hairless guinea pigs transdermally. Quantitative skin irritation measurements were obtained by monitoring erythema by skin color reflectance with the Minolta Chromameter. Antiflammin 1 delivered by iontophoresis significantly decreased, but did not eliminate, the erythema associated with co-delivery of an irritating drug compound. Lesion formation was also reduced in the presence of antiflammin 1. In vitro flux across hairless guinea pig skin demonstrated no significant differences in flux of the irritant compound in the presence or absence of antiflammin 1. In vivo generation and efflux of the inflammation mediator Prostaglandin E2 increased during 24-h application of irritant and was unchanged in the presence of antiflammin 1. This result is discussed with respect to recent evidence that antiflammins may act on the lipo-oxygenase pathway. In summary, antiflammin 1, an anti-inflammatory peptide, can be delivered transdermally by iontophoresis with retention of its biological activity in vivo.