The possible modulating effect of previous nickel sensitization on subsequent cobalt sensitization, and vice versa, was studied in a guinea pig model, using an open epicutanous induction protocol. Challenge tests were made by both topical and systemic routes. Controls included animals sensitized to only one of the metals. Animals sensitized with both metals seemed to react more readily in patch testing to either allergen, as compared to mono-sensitized animals. Systemic challenge with cobalt revealed a significantly (p less than 0.05) higher reaction rate (70%) in animals originally sensitized to cobalt and subsequently to nickel, as compared to the reaction rate (20%) in cobalt mono-sensitized animals. The reverse order of double-sensitization (nickel first, cobalt subsequently) led to an intermediate cobalt sensitization rate (50%). These experimental data corroborate clinical findings which have indicated a mutual enhancing effect of nickel and cobalt contact sensitization in man, and provide an animal model for studying the underlying immunological processes.