Six patients with mycosis fungoides were treated with topical mechlorethamine hydrochloride for periods of 2-4 yr. Clinical and histological studies for radiomimetic and radiodermatitis-like effects failed to demonstrate any abnormalities. The only observed changes were generalized hyperpigmentation of the skin and melanin-containing melanophages in the papillary dermis. The long-term use of topical mechlorethamine may be a safe form of therapy, but a continuous indefinite follow-up of patients on this medication should be mandatory.