We examined the plasma and saliva levels of methotrexate (MTX) achieved during the treatment and rescue periods of ten patients receiving 42-h MTX infusions followed by citrovorum rescue. Saliva MTX levels were generally 1%--2% of the simultaneous plasma levels. Four patients developed severe oral mucositis; three patients developed mild to moderate oral toxicity, and three others had no evidence of mucositis. MTX levels in the patients with severe mucositis were not higher and did not persist longer than the levels achieved in patients with mild or absent toxicity. Attempts at reducing the severity of oral mucositis with topical citrovorum mouthwashes or with atropine to suppress salivation were unsuccessful. MTX-induced oral mucositis is not related to salivary MTX concentrations, and the use of topical citrovorum therapy or the suppression of salivation does not appear to ameliorate this toxicity.