In a study to evaluate its acnegenic potential, increasing concentrations of 1,2,4-trichlorobenzene were applied topically to the ventral surface of the rabbit ear three times weekly for 13 weeks. Additional groups of rabbits received similar treatment with petroleum ether (solvent controls), received no treatment (negative controls), and received four once-weekly treatments with hexachlorodiphenyloxide, a known chloracnegenic agent (positive controls). Skin response to 1,2,4-trichlorobenzene was characterized grossly by dermal irritation directly related to the concentration of test material; there were the associated histologic changes of acanthosis and hyperkeratosis; there was no primary follicular involvement characteristic of acneform dermatitis. Dermal responses to hexachlorodiphenyloxide consisted of gross follicular enlargement, with waxy excretion on pressure, and severe scaling. The affected ear appeared thickened up to three times normal size and histologic sections showed primary follicular involvement characterized by marked thickening of the sheath and marked distention of the follicles with keratin, with resultant comedone formation, typical of chloracne.