In a study of zoonotic cutaneous leishmaniasis (CL) due to leishmania major in an endemic focus in Saudi Arabia, lymph node enlargement was observed in 66 of 643 patients (10.26%). The epitrochlear lymph nodes were most commonly involved (68%), but cervical (11%), axillary (15%), and inguinal (18%) lymph nodes were also involved. In eight patients (12%), two lymph node areas were involved. The affected lymph nodes were typically solitary, firm, mobile, nontender, only moderately enlarged, and appeared to persist beyond the clinical healing of the associated skin lesions. The results of pathologic and immunopathologic studies carried out on eight lymph nodes obtained from this group of patients supported the leishmanial etiology. Although amastigotes were only demonstrated in two lymph nodes, the leishmanial antigen was found in all eight specimens. The lymph node involvement is another manifestation of dissemination in infection with a dermotropic leishmania. It appears that in some cases, instead of the parasite, it may be the leishmanial antigen that disseminates and produces lymphadenitis.