The ability of a chemical to cause contact sensitization has traditionally been evaluated in animal models typically using the guinea pig. However, these methods are expensive and require subjective analysis of erythema, which makes evaluation of dyes difficult. The mouse ear swelling test (MEST) is a more quantitative and less costly method, but it has not always been reliable for the detection of moderate and weak sensitizers. To identify a MEST that can reliably detect weak sensitizers, several published MEST procedures were examined using the strong sensitizer 2,4-dinitrofluorobenzene (DNFB) and three weaker sensitizers, glutaraldehyde, formalin, and an azo dye (Solvent Red 1 (SR1)). Almost all variations of the MEST procedures detected the strong sensitizer (DNFB) after optimizing the chemical concentration and sensitizing procedure; however, only one protocol detected the weaker sensitizers, glutaraldehyde, formalin, and SR1. This sensitive MEST protocol required test animals to be fed a vitamin A-supplemented diet for 4 weeks prior to sensitization. (Copyright (c) 1993 Raven Press, Ltd., New York.)