The photoallergic potential of various compounds was assessed using a mouse ear-swelling model, which offers the advantage of being quantifiable and more objective than models based on subjective evaluation of erythematous skin reactions. Cyclophosphamide pretreated BALB/c mice were induced by topical treatment of the dorsal skin surface on 3 consecutive days and challenged on the ears 5 days after the last induction. For each induction and challenge treatment, mice were consecutively irradiated with ultraviolet (UV) A (10 J/cm2) and UVB (45 mJ/cm2) radiation 30 min to 1 hr after test material application. The photoallergic response to musk ambrette, a known human photoallergen, was significantly augmented when three consecutive induction exposures were used as compared with one or two inductions. The photoallergic potential of nine other known human photoallergens (tetrachlorosalicylanilide, bithionol, 6-methylcoumarin, chlorpromazine, sodium omadine, bisphenol A, sulphanilamide, fentichlor and p-aminobenzoic acid) was successfully detected using the mouse model. In each experiment, the ear thickness changes observed in the photoallergy test mice were significantly greater than the changes observed in the contact allergy, vehicle/radiation and phototoxicity control mice. Coumarin and homosalate, two agents not traditionally associated with causing photoallergy in humans or animals, did not demonstrate contact photoallergy using this model. With three of the photoallergens, musk ambrette, bithionol and tetrachlorosalicylanilide, the ear swelling response obtained was due to photoallergy alone and not due to the co-existence of both contact photoallergy and contact allergy. In addition, irradiating mice 24 hr, rather than 1 hr, following application of the test material during the induction phase resulted in a significantly reduced photoallergic response with both musk ambrette and tetrachlorosalicylanilide. These results indicate that the mouse ear-swelling model is a potentially useful model for investigative and predictive photoallergy testing.