Two patients receiving low dose methotrexate, one with rheumatoid arthritis and the other with pityriasis rubra pilaris, developed disseminated histoplasmosis and Mycobacterium avium intracellulare pneumonia, respectively. Twenty-three cases of opportunistic infection in patients receiving low dose methotrexate have been reported previously, with Pneumocystis carinii pneumonia being the most common infection (10 of 23, 43%). Patients receiving low dose methotrexate are at risk for opportunistic infection despite normal leukocyte counts.